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The Effect of Multispot Laser Panretinal Photocoagulation on Retinal Sensitivity and Driving Eligibility in Patients With Diabetic Retinopathy

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... Repeated supplemental PRP is associated with permanent sequelae on visual function including final visual acuity below the driving standard, restricted visual fields that preclude driving, night vision difficulties, loss of colour vision and reduced contrast sensitivity, and increased macular oedema. [3][4][5][6][7] Although laser technology and techniques have evolved over the past decade to reduce side-effects, 5,6 approximately 4·5% progress to require vitrectomy surgery. 8 Therefore, there is a substantial unmet need for novel treatments that reduce the risk of severe visual loss in PDR that is non-inferior to PRP with fewer side-effects. ...
... Repeated supplemental PRP is associated with permanent sequelae on visual function including final visual acuity below the driving standard, restricted visual fields that preclude driving, night vision difficulties, loss of colour vision and reduced contrast sensitivity, and increased macular oedema. [3][4][5][6][7] Although laser technology and techniques have evolved over the past decade to reduce side-effects, 5,6 approximately 4·5% progress to require vitrectomy surgery. 8 Therefore, there is a substantial unmet need for novel treatments that reduce the risk of severe visual loss in PDR that is non-inferior to PRP with fewer side-effects. ...
... 21 With advances in laser technology and techniques, there are reports with a short follow-up suggesting that modern-day laser techniques and technology such as multispot laser have reduced the prevalence of visual field loss with PRP. 6,22,23 However, our study shows that despite 69% of the study cohort being treated with multispot laser, aflibercept is associated with lower risk of visual field loss than with a modern day laser at 52 weeks, in keeping with findings noted in the ranibizumab trial 10 in PDR at 2 years. ...
Article
Background: Proliferative diabetic retinopathy is the most common cause of severe sight impairment in people with diabetes. Proliferative diabetic retinopathy has been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We report the 1 year safety and efficacy of intravitreal aflibercept. Methods: In this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged ≥18 years) with type 1 or 2 diabetes and previously untreated or post-laser treated active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic centres. Patients were randomly assigned (1:1) to repeated intravitreal aflibercept (2 mg/0·05 mL at baseline, 4 weeks, and 8 weeks, and from week 12 patients were reviewed every 4 weeks and aflibercept injections were given as needed) or PRP standard care (single spot or mutlispot laser at baseline, fractionated fortnightly thereafter, and from week 12 patients were assessed every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by minimisation with a web-based computer generated system. Primary outcome assessors were masked optometrists. The treating ophthalmologists and participants were not masked. The primary outcome was defined as a change in best-corrected visual acuity at 52 weeks with a linear mixed-effect model that estimated adjusted treatment effects at both 12 weeks and 52 weeks, having excluded fluctuations in best corrected visual acuity owing to vitreous haemorrhage. This modified intention-to-treat analysis was reapplied to the per protocol participants. The non-inferiority margin was prespecified as -5 Early Treatment Diabetic Retinopathy Study letters. Safety was assessed in all participants. This trial is registered with ISRCTN registry, number 32207582. Findings: We recruited 232 participants (116 per group) between Aug 22, 2014 and Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group) contributed to the modified intention-to-treat model, and 210 participants (104 in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was non-inferior and superior to PRP in both the modified intention-to-treat population (mean best corrected visual acuity difference 3·9 letters [95% CI 2·3-5·6], p<0·0001) and the per-protocol population (4·0 letters [2·4-5·7], p<0·0001). There were no safety concerns. The 95% CI adjusted difference between groups was more than the prespecified acceptable margin of -5 letters at both 12 weeks and 52 weeks. Interpretation: Patients with proliferative diabetic retinopathy who were treated with intravitreal aflibercept had an improved outcome at 1 year compared with those treated with PRP standard care. Funding: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.
... The most universal requirement for maintaining an unrestricted driver's license in the United States is based on VA of 20/40 or better in one or both eyes together 20 . Though there are a number of other criteria for a patient to drive 21,22 , determining the ability for an eye to achieve ≥ 20/40 is useful for counseling patients. In the United States, VA loss due to diabetic retinopathy in one eye keeps many commercial drivers (e.g. ...
... As discussed, these surgical outcomes have a large socioeconomic impact on the country with respect to commercial drivers. There are other factors that could limit driving function in patients with PDR beyond loss of VA such as loss of peripheral field from PRP 21,22,35,36 ; a limitation to this study is that we did not include assessment of VFQ-25 or visual fields. We also did not analyze the status of the fellow eye, which may or may not have been good enough to meet the vision minimum for driving. ...
Article
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Most patients needing diabetic tractional retinal detachment (TRD) surgery are working-age adults that drive and participate in other vision-dependent activities of daily living. We sought to determine the proportion of patients that achieve functional visual acuity (VA) based on the World Health Organization (WHO) definition of 'low vision' (≤ 20/80) and US driving standards (≥ 20/40) after vitrectomy for diabetic TRD. In this 10-year retrospective review, consecutive patients who underwent primary vitrectomy for TRD from proliferative diabetic retinopathy were studied. 240 eyes in 203 patients met criteria for analysis (38 eyes were lost to follow up at 3 months; 68 at 12 months; 146 at 60 months). While most patients (nearly 80%) having TRD surgery had low vision pre-op, almost half attained VA that was > 20/80 five years post-op. Those most likely to achieve significant visual improvement (p < 0.0001) had concomitant vitreous hemorrhage pre-op. Only 6% of eyes met the US minimum driving standard before surgery based on VA compared to 28% after vitrectomy however this study did not examine visual fields which could warrant additional assessment depending on local requirements. In summary, significant gains in visual acuity are seen after vitrectomy for diabetic TRD that can result in functional improvement in activities of daily living.
... Sivaprasad et al. [9] found an LTFU rate of 4% at 1 year (excluding deaths, randomization in errors, and exclusion due to eligibility after enrollment). In contrast, Subash et al. [10] found an LTFU rate of 12% at 6 months. Furthermore, Obeid et al. [11] reported an LTFU rate that exceeded 20% at 4 years in a retrospective cohort study. ...
... In addition, patients receiving IVIs are generally more satisfied with treatment than patients receiving PRP or a combination of interventions [8,9,18]. In addition to being painful, PRP is also associated with an increased risk of macular edema, peripheral visual field loss, and vitreous hemorrhage [8][9][10]19], which leads to lower patient satisfaction as shown in our results. Our results also showed a positive correlation between the number of IVIs and treatment unaffordability; this may explain the higher LTFU rate in subjects who underwent both PRP and IVI. ...
Article
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Purpose. This study determined the clinical impact and causes of loss to follow-up (LTFU) from the patients’ perspective in individuals with proliferative diabetic retinopathy (PDR) who received panretinal photocoagulation (PRP) and/or intravitreal injections (IVIs) of antivascular endothelial growth factor (VEGF). Methods. This prospective cohort study included 467 patients with PDR who received PRP and/or IVIs of anti-VEGF between May 2013 and June 2018. LTFU was defined as missing any follow-up visit for any interval exceeding 6 months, provided that patients eventually resumed care. Main outcome measures include rates and causes of LTFU. Results. A total of 391 patients (83.7%) were followed up, and 76 patients (16.3%) were LTFU over the study period. Rates of LTFU decreased with age (P=0.005). Questionnaire analysis conducted for patients’ LTFU showed a significant positive correlation between best corrected visual activity (BCVA) loss and patient’s lack of trust and satisfaction with treatment (rs = 0.458, P
... signals. However, the ERG changes found after retinal photocoagulation-slightly greater b-than a-wave amplitude reduction-might indicate that the treatment might not only destroy the retinal areas directly illuminated by the laser beam, but also affect the functional integrity of adjacent areas, as previously hypothesized [19,25], as far as in the macula [26]. These observations could also explain reduction in cone-driven ERG responses after PDR [19] and are certainly undesirable side effects of the laser treatment. ...
... Of interest, data and other reports [13] suggest that PASCAL is as effective as conventional PRP in the treatment of PDR, and it has been suggested that PASCAL laser burns cause less inner-retinal destruction [25] and minor retinal sensitivity loss, with consequent only mild visual field changes detected at 6 months after treatment [26]. However, although ERG changes found on group PASCAL were slightly milder than on group ETDRS, difference between groups was not statistically significant, probably due to the small sample. ...
Article
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Purpose To compare retinal function changes in eyes with proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab (IVR), combined or not with conventional (ETDRS) or multispot laser panretinal (PASCAL) photocoagulation (PRP). Methods This study included laser-naive PDR patients that required PRP. Eyes were randomly and prospectively assigned to receive IVR or IVR combined with PASCAL or EDTRS. PRP was performed at baseline in 1 (PASCAL) or 2 (ETDRS) sessions. In eyes with macular edema, macular short pulse grid laser was associated with IVR at baseline and IVR was repeated monthly or quarterly if neovascularization was detected on angiography. Comprehensive ophthalmological evaluations, including SD-OCT, were performed at baseline and every 4 weeks after treatment. Full-field electroretinography (ERG: extended ISCEV standard) was performed at baseline and at 12, 24 and 48 weeks. Results IVR = 13, PASCAL = 15 and ETDRS = 15 eyes finished 48-week follow-up. There was a statistically significant BCVA improvement of 0.1–0.3 logMAR in all groups, and fluorescein angiography leakage area (FLA) reduced in 56%, 73%, and 73% from baseline for ETDRS, IVR and PASCAL, respectively, up to 48 weeks without significant differences between groups (p > 0.05). A significant a- and b-wave amplitudes reduction was observed for dark- and light-adapted ERG for ETDRS and PASCAL, but only minor dark-adapted b-wave reduction was found for IVR, up to 48 weeks. As an example, at week 48, combined response b-wave amplitude reduced in 181.5 ± 31.4 µV, 128.0 ± 27.9 µV and 82.4 ± 15.2 µV for ETDRS, PASCAL and IVR (p < 0.05 each group), respectively. No significant difference was observed between ETDRS and PASCAL for any ERG parameter. Conclusions IVR combined with single or multiple spot PRP causes similar retinal function impairment during 48 weeks of observation, while IVR alone seems to be similarly effective controlling FLA without changing retinal function.
... 17,18,20 Diabetes After AMD, diabetes is the most studied pathology by MP, probably due to its significant incidence in the general population, but also because MP provides a comprehensive and precise examination of sensitivity in diabetic vascular problems. Different MP applications have been described in the peer-reviewed literature for diabetic patients, such as the characterization of anatomical and functional changes, 31-35 comparison of pre-and post-medical or surgical treatment, [36][37][38][39][40][41][42] or the study of eye fixation. 31,43 The characterization of anatomical and functional changes in diabetes through MP differs from the study of sensitivity losses caused by ischemia due to capillary drop-off, 31 the loss of sensitivity in macular-induced diabetic edema, 32,33 or the study of anatomical alterations as microcysts 33,34 or hard exudates. ...
... Some of them have been analyzed by MP in order to evaluate the changes before and after their prescription, such as flavonoids and vitamins, 36,37 anti-VEGF injections, 38,39 or dexamethasone implants, 40 as well as to evaluate the effect of these treatments over time. 36,40 MP has also been used to study some surgical treatments, such as pan-retinal laser photocoagulation, with the objective of quantifying the reduction on sensitivity 41 and for comparison purposes. 38,42 Regarding the stability and location of fixation, a correlation between the stability of fixation and other parameters, such as BCVA, 31,43 the presence of central scotomas, 43 or anatomical findings, has been detected. ...
Article
Microperimetry (MP) is a technology that allows the study of retinal sensitivity at different foveal and parafoveal areas as well as eye fixation. It is a technique of functional evaluation, providing a direct correlation between anatomical and functional outcomes. There are a great variety of studies which evaluate the repeatability or reliability of measurements obtained with this technology and also describe and explore different clinical applications. MP has been shown to be useful in the characterization of sensory and motor conditions, such as amblyopia or nystagmus. Concerning ocular pathology, several studies have confirmed the usefulness of MP for evaluating and analyzing different retinal pathological conditions, such as age-related macular degeneration or glaucoma, and for analyzing the effect of different medical or surgical treatments for these conditions. MP has also been shown to be useful for visual training or rehabilitation in some specific cases.
... Past studies have reported the degree of peripheral retina destroyed by photocoagulation; however, none have documented progressive long-term visual field loss over a 2-year time period. 5,35,36 With the unreliable grading of the optic nerve and further progressive deterioration of visual fields post laser, it is understandable why some diabetic patients post PRP are being misdiagnosed with having normal-tension glaucoma despite the presented symptoms that are likely attributed to iatrogenic effects of the laser. ...
... Studies 5,36 have previously reported visual field changes following PRP, but no study has looked at the progressive nature over a 2-year time period. The progressive improvement in ischemia following PRP is also a novel finding. ...
Article
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PurposeTo evaluate long-term structural and functional changes to the retina and optic nerve following panretinal photocoagulation (PRP) in diabetic retinopathy (DR) patients.Methods Participants were patients with DR requiring PRP and control patients with DR not requiring PRP. The Heidelberg retinal tomography (HRT) and optical coherence tomography (OCT) were performed to analyze the optic nerve and macula. Best-corrected visual acuity (BCVA) and visual field (VF) testing were done to measure central and peripheral vision. Wide-field fluorescein angiogram was performed to monitor the progression of diabetic ischemia. The primary outcome measure was to determine the degree of retinal and optic nerve changes before and after PRP.ResultsThere was a non-significant thickening of the macula and retinal nerve fiber layer at 6 months post laser that recovered by 24 months. Mean perfused ratio was significantly increased (P=0.02) at 12 and 24 months post laser. Independently grading patient stereophotographs, grader 1 indicated there was a non-significant increase in cup to disk ratio post laser, while grader 2 indicated a significant increase at 6 (P=0.04), 12 (P=0.02), and 24 months (P=0.005). There was a significant VF decrease (P≤0.02) at 12 and 24 months post laser with BCVA showing a non-significant trend of deteriorating results.Conclusion Despite an improvement in peripheral perfusion, there was a significant progressive decline of peripheral VF over the study period. Clinical grading of the optic nerve was more unreliable following PRP, despite the absence of significant morphological changes as detected by the OCT and HRT.Eye advance online publication, 28 April 2017; doi:10.1038/eye.2017.66.
... Může dojít i ke vzniku nebo k progresi DME [59,60] a ke snížení kontrastní citlivosti [58,61,62], k poškoze-ní zadních ciliárních nervů vedoucích k dilataci zornice a k poruchám akomodace [63]. PRP však i přes tyto nevýhody zůstává velmi klíčovou součástí léčby pokročilé formy NPDR a PDR. ...
Article
Diabetic retinopathy is one of the most common complications of diabetes mellitus and represents a serious health, social and economic problem. With the expected increase in the number of patients with diabetes, it is becoming the leading cause of severe vision loss in the working-age population. The presented guidelines summarize the current knowledge about this disease in order to standardize and update the procedures for the diagnosis, classification and treatment of diabetic retinopathy.
... The most commonly used modes of laser treatment for macular edema are focal, grid and modified grid. In focal treatment, microaneyrysms causing macular edema are treated directly; in grid treatment, the areas of diffuse capillary leakage and of capillary non perfusion are lasered in a grid pattern; a modified grid is a combination of focal and grid treatment [4][5][6]. The aim of this study is to determine the effect of laser photocoagulation on preventing vision loss and on the resolution of macula edema in retinal vascular diseases. ...
Article
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Due to the significance of macular edema in retinal vascular diseases, this study aims to determine whether laser photocoagulation is effective in the treatment of macular edema and in the improvement of visual acuity. This is a prospective data study considering 80 patients with 52 eyes, with a follow-up of 6 weeks, 3 months, and six months with macular edema treated with double frequency yag laser photocoagulation in Aso Eye Hospital in Sulaymaniyah City, Kurdistan, Iraq, from February 2010 to October 2010. With six months of follow-up, visual acuity was improved in 36.4% of eyes, unchanged in 61.3%, and worsened in 2.3%. After this period the macular edema was improved in 78.85% and not improved in 21.15%. According to this study, baseline visual acuity and retinopathy severity were two important intervening factors in response to laser therapy. Comparing the current results with other studies, it has been found that, in assessing visual outcomes, laser photocoagulation is an effective modality in the treatment of macular edema, and it improves visual acuity in retinal vascular diseases.
... For the advanced phases of retinal vascular diseases, retinal laser photocoagulation can be conducted to seal the ischemic retinal non-perfusion zone other than the macula and destroy new retinal vessels to prevent severe vision-impaired complications, such as vitreous hemorrhage and retinal detachment [123]. However, some adverse effects limit its application, including aggravated macular edema, impaired peripheral visual field, nyctalopia, and reduced retinal sensitivity [124]. In addition, pars plana vitrectomy is the only option to improve the vision of patients with persistent vitreous hemorrhage (VH) or tractional retinal detachment (TRD), although a significant proportion of patients regain poor vision shortly after vitrectomy as a result of various reasons, including aggravated cataract, inflammatory irritated epiretinal membrane (ERM) formation, recurrent VH, and RD [125][126][127]. ...
Article
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Retinal vascular disease is a highly prevalent vision-threatening ocular disease in the global population; however, its exact mechanism remains unclear. The expansion of omics technologies has revolutionized a new medical research methodology that combines multiple omics data derived from the same patients to generate multi-dimensional and multi-evidence-supported holistic inferences, providing unprecedented opportunities to elucidate the information flow of complex multi-factorial diseases. In this review, we summarize the applications of multi-omics technology to further elucidate the pathogenesis and complex molecular mechanisms underlying retinal vascular diseases. Moreover, we proposed multi-omics-based biomarker and therapeutic strategy discovery methodologies to optimize clinical and basic medicinal research approaches to retinal vascular diseases. Finally, the opportunities, current challenges, and future prospects of multi-omics analyses in retinal vascular disease studies are discussed in detail.
... Empirically, one might expect a close relationship between the total burn area and the degree of visual-field loss. This might explain why more recent studies of PRP with modern multispot lasers have shown none or very mild visual-field loss [8,9]. ...
Article
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The purpose of this study was to compare driving-simulator performance of participants with visual-field loss (VFL) from panretinal photocoagulation (PRP) of proliferative diabetic retinopathy (PDR) with a normally sighted control group. Furthermore, we investigated the effects of VFL of different extent on driving. Data on performance and safety from a traffic-simulator test for 27 participants with VFL from PRP of PDR were retrospectively compared with data from 83 individuals without visual deficits in a cross-sectional study. Individuals with diabetes that regained their driving licences after a successful simulator test were then followed in a national accident database. Diabetes participants passed the test in 56% of the cases. Compared with the control group, diabetes participants had more risky “failed to give way” events and longer reaction times. Failed diabetes participants had lower mean sensitivity in the superior visual field than those who passed. None of the participants with a regained licence were involved in a motor vehicle accident during the 3–6-year follow-up after the simulator test. Diabetes participants had worse performance and safety than the controls. However, even individuals with VFL from PRP might drive safely, which highlights the need for individual assessments in licencing issues.
... The GATE algorithm is as fast as the SITA Standard and has a validity and precision comparable to the normal 4-2-1 strategy. Octopus 900 perimetry using the GATE strategy has become the most commonly used device for clinical studies and treatment trials for IRD. 15 55 58 59 The Octopus system allows (1) use of custom colour test targets; (2) a validated, retina-specific optimised testing strategy to be employed, that is, GATE; and arguably most importantly, (3) exportation of all raw retinal sensitivity data, which can then be comprehensively and robustly analysed using Visual Field Modelling and aAnalysis (VFMA) methodology (figure 1), 60 from which topographic displays and hill-of-vision volumetric outputs can be derived, including the total hill-of-vision (V TOT ) or any subset, for example, the central 30° field of vision (V 30 ). 52 These volumetric analyses afforded by VFMA can be applied equally as well to VF data obtained from microperimetry (MP), 22 61 62 potentially allowing game-changing state-of-the-art retinal function evaluation in IRD and other retinal diseases, 63 and enabling incorporation of all data in a non-biased fashion, truly representing the full impact of disease natural history or treatment effect. Assessment of retinal sensitivity using VFMA with creation of volumetric endpoints, such as V TOT , V 30 , V 10 and V 3 , allow direct comparison of values between subjects, at different regions with a given test, and between baseline and follow-up testing. ...
Article
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Functional assessments are a fundamental part of the clinical evaluation of patients with inherited retinal diseases (IRDs). Their importance and impact have become increasingly notable, given the significant breadth and number of clinical trials and studies investigating multiple avenues of intervention across a wide range of IRDs, including gene, pharmacological and cellular therapies. Moreover, the fact that many clinical trials are reporting improvements in vision, rather than the previously anticipated structural stability/slowing of degeneration, makes functional evaluation of primary relevance. In this review, we will describe a range of methods employed to characterise retinal function and functional vision, beginning with tests variably included in the clinic, such as visual acuity, electrophysiological assessment and colour discrimination, and then discussing assessments often reserved for clinical trials/research studies such as photoaversion testing, full-field static perimetry and microperimetry, and vision-guided mobility testing; addressing perimetry in greatest detail, given it is commonly a primary outcome metric. We will focus on how these tests can help diagnose and monitor particular genotypes, also noting their limitations/challenges and exploring analytical methodologies for better exploiting functional measurements, as well as how they facilitate patient inclusion and stratification in clinical trials and serve as outcome measures.
... Furthermore, the retinal break may not be securely sealed that reopening of the breaks may happen postoperatively. Besides, for some breaks develop very posteriorly within the vascular arcade, laser photocoagulation at posterior poles would lead to permanent visual field defects 10,11 , and progressive enlargement of laser scars with subsequent involvement of the central visual field is another concern. ...
Article
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To describe the surgical outcomes of using human amniotic membrane (hAM) grafts in the management of retinal breaks in diabetic tractional detachment (TRD) and combined tractional and rhegmatogenous retinal detachment (CTRRD). A retrospective case series of 10 eyes with TRD or CTRRD receiving pars plana vitrectomy with hAM grafts implantation, compared with 13 controls receiving the same surgery without hAM grafts. Best-corrected visual acuity (BCVA) and re-detachment rate were compared between two groups. Postoperatively, all eyes in the hAM group had retina attachment without recurrence, while 9 eyes in the control group had retina re-detachment and required additional surgery (0% vs 69.2%, p = 0.003). The BCVA significantly improved in the hAM group (from 1.96 ± 0.95 to 1.44 ± 0.77 in log MAR, p = 0.03), but not improved in control group (p = 0.20). Postoperative optical coherence tomography of the eyes receiving hAM grafts demonstrated glial tissue regeneration and restoration of ellipsoid zone. In diabetic TRD or CTRRD, hAM grafts could be an effective method, with promising outcome. Compared to standard surgery, it could result in higher retina reattachment rate and significant visual improvement. Moreover, it may offer the adjunctive benefit in tissue regeneration and fasten ellipsoid zone restoration.
... The evolution of lasers from conventional to a diversity of multispot and subthreshold systems, capable of reducing exposure times and using different wavelengths with different absorption spectra, has increased the options of treatment strategies, presenting different potential for harm and theoretically less impact on daily life activities; 6 however, data available in the literature regarding the effects of PRP is limited mainly due to small sample sizes, short follow-up periods and the evaluation of treatments with non-standardised parameterizations. ...
Article
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Purpose To address the long-term visual function after bilateral pan-retinal photocoagulation (PRP) and its impact in real life, namely on visual field (VF) legal criteria to drive. To determine potential predictors related to clinical factors and treatment strategies. Patients and Methods Observational cross-sectional study. Eyes from diabetic patients diagnosed with diabetic retinopathy who underwent bilateral PRP, with or without macular treatments and with visual acuity legal criteria for non-professional driving were randomly assigned. Main outcomes were: demographic and clinical data including best corrected visual acuity; binocular visual field (EBST-Esterman Binocular Suprathreshold Test, Humphrey analyzer3®); contrast sensitivity (CS-Metrovision-MonPack3®); light scattering in the retina (HD Analyzer, Visiometrics®). Results Seventy-one diabetic patients included (44 men and 27 women), with a mean age of 62.2±11.8 years. PRP was performed, on average, 9.7±6.9 years before the study. The average EBST Score was 85.8±17.0 and the average CS (2–5cpd) was 19.5±2.9 dB in photopic and 14.2±4.1 dB in mesopic conditions. Through a multivariate regression model, after adjusting to the clinical and demographic factors as possible confounders, we found that treatment factors associated with worse results were the use of Argon laser for the EBST Score, the very confluent PRP for the number of non-viewed points in the central 30°x20° of the EBST and the presence of macular treatments for the CS tests. According to Portuguese law, 79% (n=56) of patients had minimal EBST amplitudes for non-professional driving. Conclusion The functional results achieved in our sample are compatible with an active life, allowing most of the patients included to overcome the requirements of Portuguese legislation for driving light vehicles, namely at the level of the binocular visual field. These results highlight the role of PRP in the treatment of diabetic retinopathy in an era with evolving less aggressive laser options.
... With the increase in the average life expectancy and the increase in the prevalence of RD in increasingly younger patients, now and in the future, more diabetic patients with PRP will be in systemic conditions compatible with an active life. Additionally, the evolution of conventional lasers to the various multispot systems, with possibilities of reducing exposure times and using different wavelengths with different absorption spectra, is increasing the number of treatment strategies, decreasing the potential for harm [6]. For these reasons, this theme will take on particular relevance. ...
... 9 Panretinal photocoagulation (PRP) is the standard treatment for sNPDR and PDR. 9 However, PRP reduces the risk of severe visual loss by only 50% and might cause some adverse effects, including peripheral visual field loss that precludes driving, nyctalopia, reduced retinal sensitivity and aggravated macular oedema that leads to vision impairment. 10 Therefore, alternative treatments that would reduce the risk of progression of sNPDR to PDR, but with fewer adverse effects, are highly desirable. ...
Article
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Introduction Diabetic retinopathy (DR) is the main cause of adult visual impairment worldwide. Severe non-proliferative DR (sNPDR) is an important clinical intervention stage. Currently, panretinal photocoagulation (PRP) is the standard treatment for sNPDR. However, PRP alone cannot completely prevent NPDR progression. One explanation might be that PRP does not remove the detrimental vitreous that plays an important role in DR progression. Microinvasive pars plana vitrectomy (PPV) was shown to be a safe and effective method to treat late-stage proliferative DR (PDR) by completely removing the pathological vitreous. However, whether PPV is effective in controlling sNPDR remains unknown. In this trial, we aim to compare the effectiveness of microinvasive PPV with that of PRP for sNPDR progression control. Methods and analysis This single centre, parallel group, randomised controlled trial aims to evaluate the clinical efficacy of microinvasive PPV in preventing the progression of sNPDR compared with PRP. A total of 272 adults diagnosed with sNPDR will be randomised 1:1 to the microinvasive PPV and PRP groups. The primary outcome is the disease progression rate, calculated as the rate of sNPDR progressed to PDR from baseline to 12 months after treatment. The secondary outcomes include the change in best-corrected visual acuity, re-treatment rate, diabetic macular oedema occurrence, change in central retinal thickness, change in the visual field, cataract occurrence and change in the quality of life. Ethics and dissemination The Ethics Committee of Zhongshan Ophthalmic Center approved this study (2019KYPJ108). The results will be presented at scientific meetings and submitted for publication to peer-reviewed journals. Trial registration number NCT04103671 .
... Ranibizumab is a recombinant, humanized, monoclonal antibody fragment that selectively binds and inhibits all active forms of vascular endothelial growth factor (VEGF)-A, the angiogenic protein responsible for NV in many ischaemic retinal diseases including PDR (Aiello et al. 1995). Evidence suggests that anti-VEGF therapy could complement or even replace the use of PRP in PDR (Fong et al. 2007;Subash et al. 2016). Previous randomized clinical trials have found that ranibizumab is at least as effective as PRP in patients with PDR and results in fewer sideeffects such as worsening of visual field, development of macular oedema or the need for vitrectomy, in addition to its strong safety profile (Writing Committee for the Diabetic Retinopathy Clinical Research Network 2015; Figueira et al. 2016). ...
Article
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Purpose: Panretinal photocoagulation (PRP) is the current standard of care in proliferative diabetic retinopathy (PDR). However, treatment with anti-vascular endothelial growth factor agents might offer better patient outcomes with fewer side-effects. The PRIDE study aimed to assess the efficacy and safety of ranibizumab with or without PRP compared with PRP alone in patients with PDR. Methods: A total of 106 PDR patients without diabetic macular oedema were randomized to receive ranibizumab 0.5 mg monotherapy (n = 35), PRP (n = 35) or combined ranibizumab 0.5 mg/PRP (n = 36). The primary objective of this 12-month, multicentre, phase II study was to investigate the change in area of retinal neovascularization (NV). Complete regression of leakage and best-corrected visual acuity (BCVA) were key secondary end-points. Results: At Month 12, there was a statistically significant difference of -2.83 mm² in the least square mean change in NV area between the ranibizumab monotherapy and PRP group, favouring ranibizumab (95% CI [-5.45; -0.21], p = 0.0344). At Month 3, 67%/0%/67% of the patients in the ranibizumab/PRP/combination groups, respectively, showed complete regression of leakage from NVs, while at Month 12, 28%/8%/18% showed complete regression of leakage from NVs. BCVA change was greater in the ranibizumab group compared with the PRP monotherapy group at Month 12 (+1.6 letters; 95% CI [-2.3; 5.5] versus -3.9 letters; 95% CI [-7.8; -0.1], p = 0.0495). Conclusions: Ranibizumab monotherapy is an alternative treatment option to laser treatment in patients with PDR. Ranibizumab showed stronger effects on NV leakage and area reduction while offering better visual acuity results than PRP alone.
... This diagnostic tool creates hill of vision (HOV) sensitivity surfaces, provides interactive three-dimensional HOV maps for visualization, and provides a unified framework for volumetric visual field analysis [51][52][53]. VFMA is widely distributed for clinical and research purposes and has been used for several clinical trials investigating both the natural history and clinical trials assessing the response to gene therapy of X-linked juvenile retinoschisis, achromatopsia, LCA, choroideremia, Stargardt disease, and Usher syndrome [31,[54][55][56][57][58][59][60][61][62], and oral valpro- ic acid as a treatment for autosomal dominant retinitis pigmentosa [63]. VFMA first constructs the HOV sensitivity surfaces from the x, y, z data exported from a standard automated perimeter or microperimeter. ...
Article
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Novel diagnostic tools to measure retinal function and structure are rapidly being developed and introduced into clinical use. Opportunities exist to use these informative and robust measures as endpoints for clinical trials to determine efficacy and to monitor safety of therapeutic interventions. In order to inform researchers and clinician-scientists about these new diagnostic tools, a workshop was organized by the European Vision Institute. Invited speakers highlighted the recent advances in state-of-the-art technologies for outcome measures in the field of retina. This review highlights the workshop's presentations in the context of published literature.
... The main causes of vision loss are diabetic macular oedema, diabetic optic neuropathy, retinal undefined, vitreous undefined (vitreous haemorrhage; VH), traction retinal detachment (TRD), and neovascular glaucoma [3,4]. For early-stage proliferative DR (PDR), where no TRD is detected by ultrasonography, timely pan-retinal photocoagulation (PRP) can reduce the rate of retinal neovascularization as well as the extent of the perfusion-free areas, thereby stabilizing the condition [5]. Furthermore, in DR with non-clearing vitreous undefined 1-4 months from onset, the DRVS study has demonstrated significantly better visual outcome with vitrectomy combined with intraocular retinal photocoagulation [6]. ...
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Background/objectives: The aim of this study was to evaluate the safety and efficacy of intravitreal conbercept (a recombinant fusion protein that primarily targets vascular endothelial growth factors) after vitrectomy for the management of proliferative diabetic retinopathy without tractional retinal detachment (TRD). Subjects/methods: Fifty patients with non-clearing vitreous haemorrhage (VH) due to proliferative diabetic retinopathy without TRD were enroled. They were randomly divided into control and treatment groups (25 eyes to each group) after they provided informed consent. The treatment group received intravitreal conbercept (10 mg/mL, 0.5 mg) immediately after surgery, while the control group did not. The best corrected visual acuity (BCVA) and the central retinal thickness were measured. Results: There were no significant between-group differences in baseline characteristics (P > 0.05), except in age (P = 0.003). Improvement in BCVA was significantly greater at 1, 4, 12, and 24 weeks post surgery in the treatment group than it was in the control group (P < 0.001). There were more cases in the control group who developed recurrent VH, but the recurrence rate of VH was not significantly different between the two groups at 12 and 24 weeks post surgery (P = 0.192 and 0.103). Central retinal thickness was lower in the treatment group than in the control group at 1 week (P = 0.012), 4 weeks (P = 0.01), 12 weeks (P = 0.001), and 24 weeks (P = 0.004) post surgery, which were statistically significant. Conclusions: An intravitreal injection of conbercept after vitrectomy improved visual acuity and seemed to reduce the recurrence of VH resulting in prompt visual recovery in the PDR patients.
... However, laser retinopexy around those paracentral breaks is difficult to perform in complicated cases owing to the retinal pathology. Besides, laser photocoagulation within posterior poles may lead to a certain degree of permanent visual field defects [8,9]. e inverted internal limiting membrane (ILM) flap technique has been increasingly used for refractory macular hole (MH) [10][11][12][13][14] and MHRD [15] with successful surgical outcomes and high closure rates. ...
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Purpose To describe the technique and outcomes of using either inverted or free internal limiting membrane flap in the management of retinal detachment due to paracentral retinal breaks. Methods This retrospective observational case series includes nine patients who received surgery for retinal detachment due to paracentral retinal breaks developed either from primary rhegmatogenous origin, or secondary iatrogenic retinal breaks after prior membrane peeling, or during surgery for tractional retinal detachment. Either inverted or free internal limiting membrane flaps were inserted in the identified breaks, followed by air fluid exchange and gas tamponade. Visual acuity and structural changes were evaluated. Results Nine eyes were included. One had primary rhegmatogenous retinal detachment, one had highly myopic eye with peripapillary atrophic hole, three had secondary retinal detachment after membrane peeling for foveoschisis or macular pucker, one had recurrent retinal detachment due to proliferative vitreoretinopathy, one had combination of tractional and rhegmatogenous retinal detachment, and two had iatrogenic breaks during surgery. The retinal breaks of all eyes were sealed with retina attached postoperatively. Visual acuity in logarithm of minimal angle of resolution improved from 1.18 ± 0.55 preoperatively to 0.74 ± 0.47 postoperatively (p=0.04). Conclusion Internal limiting membrane flap technique can be a surgical approach selectively for retinal detachment due to paracentral retinal breaks with difficulty for laser application. The retina can be attached successfully and achieve good visual outcome without major complication. This trial is registered with NCT03707015.
... A proportion of patients treated with repeated PRP fail the driving standards in the long term. 16,17 There is therefore an unmet need for an alternative treatment option that could either replace or delay the need for laser treatment for PDR. which stimulated growth and permeability of new vessels on the retina simulating PDR and also induced NVG. 18 There is also clear evidence that hypoxia from decreased retinal perfusion produces VEGF. ...
Article
Background Panretinal photocoagulation (PRP) has been the standard of care for patients with proliferative diabetic retinopathy (PDR) for the last 40 years. It prevents severe visual loss in PDR but is also associated with adverse effects on visual functions. Objectives The clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (CLARITY) trial evaluated the clinical efficacy, mechanisms and cost-effectiveness of intravitreal aflibercept (Eylea ® , Regeneron, Tarrytown, NY, USA/Bayer Pharma AG, Berlin, Germany therapy for PDR. Design A multicentre, prospective, individually randomised, single-masked, active-controlled trial with concurrent economic evaluation that tested the non-inferiority of intravitreal aflibercept versus standard care PRP at 52 weeks. A subset of the participants enrolled in a mechanistic evaluation substudy. Setting 22 UK NHS clinical sites. Participants Patients aged at least 18 years having either treatment-naive PDR or active retinal neovascularisation (NV) despite prior PRP requiring treatment and best corrected visual acuity (BCVA) of 54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or better in the study eye were included. Eyes with evidence of macular oedema at baseline confirmed by central subfield thickness > 320 µm on spectral-domain optical coherence tomography were excluded. Intervention In the intervention arm, intravitreal aflibercept injections were given at baseline, 4 and 8 weeks and patients were subsequently reviewed every month and injected pro re nata based on the treatment response defined by degree of regression of retinal NV. In the comparator arm, PRP was completed in 2-weekly sessions and then supplemented if necessary at 8-weekly intervals. Main outcome measures The primary outcome was the mean change in BCVA at 52 weeks utilising a linear mixed-effects model incorporating data from both week 12 and week 52. Results A total of 232 participants (116 per arm) were recruited between August 2014 and November 2015. A total of 221 and 210 participants contributed to the intention-to-treat (ITT) model and per-protocol (PP) analysis, respectively. Economic evaluation was undertaken on 202 participants (101 per arm) with complete cost and outcome data. Aflibercept was non-inferior and superior to PRP in both the ITT population [mean BCVA difference 3.9 letters, 95% confidence interval (CI) 2.3 to 5.6 letters; p < 0.0001] and the PP population (difference 4.0 letters, 95% CI 2.4 to 5.7 letters; p < 0.0001). From a public sector multiagency perspective that covers health and social care services, treatment with aflibercept costs more in terms of total resource use (mean adjusted total additional cost per patient = £5475, bootstrapped 95% CI £5211 to £5750) than PRP over a 12-month follow-up period. There were a small number of important safety events in each arm. Patients were more satisfied with aflibercept than PRP. Limitations This study is limited to 1 year of follow-up. Conclusions At an additional cost, the study shows that intravitreal aflibercept is an effective alternative treatment option for PDR in the first year. Future work Future research is needed to evaluate the long-term benefits of aflibercept in comparison with PRP and other anti-vascular endothelial growth factor agents for this condition. Trial registration Current Controlled Trials ISRCTN32207582. Funding This project was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanistic Evaluation programme, a Medical Research Council and NIHR partnership. Aflibercept was supplied by Bayer Plc (Reading, UK). The study was sponsored by NIHR Moorfields Biomedical Research Centre and supported by the UK Clinical Research Network. The research was supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, the NIHR Moorfields Clinical Research Facility and the UK Clinical Reasearch Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is partly funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London.
... Several brands of multispot laser systems are available and are claimed to allow effective, painless coagulation of the retina with reduced treatment times by one third; patients are said to be more comfortable, less inconvenienced, with decreased time requirements for the ophthalmologist. [4][5][6] We configured our multispot laser system to create a "laser line" by which 10-0 nylon sutures after filtering surgery were able to be cut more easily. We have used the technique for >50 patients. ...
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Although often uncomplicated, the current technique for laser suture lysis after filtration surgery requires patient cooperation and appropriate care taken by the surgeon. In cases with suboptimal cooperation, steadying the 50-µm laser aiming beam exactly over a thin 10-0 nylon suture, can be exhausting, difficult for both the patient and the surgeon; it may prove to be ineffective or even precipitate complications. We describe a novel method for laser suture lysis using a multispot laser system, which requires less patient cooperation and surgeon skills and yields excellent results.
... Although peripheral visual field loss in a non-study eye at baseline due to PRP could impact patient-reported outcomes, particularly in the PRP group where both eyes would have peripheral visual field loss following placement of PRP in the study eye, there were no treatment group differences identified in the peripheral vision subscales from the NEI VFQ-25 or UAB-LLQ for the subgroup of participants that had a history of PRP in their fellow eye at baseline (eTable 17). Recent work suggests that the detrimental effects of PRP on peripheral visual fields may not impact driving eligibility (by UK standards), 12 although this research did not evaluate driving safety and performance, which could be affected by visual field loss following PRP for PDR. 13 While the data from this trial clearly show a loss of visual field due to PRP, we are not able to comment on how this may affect driving eligibility. ...
Article
Purpose: Compare patient-centered outcomes in patients with proliferative diabetic retinopathy (PDR) treated with ranibizumab versus panretinal photocoagulation (PRP). Design: Randomized clinical trial. Methods: Setting: Multicenter (55 US sites). Patient population: 216 adults with one study eye out of 305 adults (excluding participants with two study eyes since each eye received a different treatment) with PDR, visual acuity 20/320 or better, no history of PRP. Intervention: Ranibizumab (0.5-mg/0.05mL) versus PRP. Main outcome measures: Change from baseline to 2 years in composite and pre-specified subscale scores from the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), University of Alabama Low Luminance Questionnaire (UAB-LLQ), Work Productivity and Activity Impairment Questionnaire (WPAIQ). Results: For the NEI VFQ-25 and UAB-LLQ composite scores, ranibizumab-PRP treatment group differences (95% CI) were +4.0 (-0.2, +8.3, P=0.06) and +1.8 (-3.5, +7.1, P=0.51) at 1 year, and +2.9 (-1.5, +7.2, P=0.20) and +2.3 (-2.9, +7.5, P=0.37) at 2 years, respectively. Work productivity loss measured with the WPAIQ was 15.6% less with ranibizumab (-26.3%, -4.8%, P=0.005) at 1 year and 2.9% (-12.2%, +6.4%, P=0.54) at 2 years. Eighty-three ranibizumab participants (97%) were 20/40 or better in at least one eye (visual acuity requirement to qualify for an unrestricted driver license in many states) at 2 years compared with 82 PRP participants (87%, adjusted risk ratio=1.1, 95% CI: 1.0, 1.2 P=0.005). Conclusions: While differences in some work productivity and driving-related outcomes favored ranibizumab over PRP, no differences between treatment regimens for PDR were identified for most of the other patient-centered outcomes considered.
Article
Many people with diabetes in the U.S. will seek or currently hold a license to drive. For many, a driver’s license is essential for everyday life. Considerable discussion has focused on whether, and the extent to which, diabetes may be a relevant factor in determining driver ability and eligibility for a license. This statement addresses such issues in relation to current scientific and medical evidence. A diagnosis of diabetes on its own is not sufficient to make judgments about an individual driver’s ability or safety. This statement provides an overview of existing licensing rules for people with diabetes in the U.S., addresses the factors that affect driving ability, identifies general guidelines for assessing driver fitness and determining appropriately tailored licensing restrictions, and provides practical guidance for health care professionals regarding clinical interventions and education for people with diabetes.
Chapter
Aqueous shunts are considered the first-line intraocular pressure-lowering surgery in the setting of neovascular glaucoma. Although aqueous shunts differ in size, material composition, and the presence or absence of a valve, they share a common design that consists of a silicone tube that shunts aqueous humor to an endplate, creating an overlying equatorial fornix-based capsule. In the setting of neovascular glaucoma, the advantages of an aqueous shunt over trabeculectomy include (1) the presence of a permanent sclerostomy (the tube); (2) aqueous drainage to the equatorial region where the potential for conjunctival scarring may be less than the limbal conjunctiva; (3) a predetermined capsular area (the endplate). This chapter will discuss the mechanisms, surgical techniques, outcomes, and complications of aqueous shunt surgery in the setting of neovascular glaucoma. Implant types described in this section include the Molteno, Krupin, Schocket, Baerveldt, Ahmed glaucoma valve, and the Ahmed ClearPath. Additionally, this chapter discusses outcomes of combined retinal treatment and aqueous shunt surgery and secondary treatment options if aqueous shunt failure occurs.
Chapter
Aqueous shunts are considered the first-line intraocular pressure-lowering surgery in the setting of neovascular glaucoma. Although aqueous shunts differ in size, material composition, and the presence or absence of a valve, they share a common design that consists of a silicone tube that shunts aqueous humor to an endplate, creating an overlying equatorial fornix-based capsule. In the setting of neovascular glaucoma, the advantages of an aqueous shunt over trabeculectomy include (1) the presence of a permanent sclerostomy (the tube); (2) aqueous drainage to the equatorial region where the potential for conjunctival scarring may be less than the limbal conjunctiva; (3) a predetermined capsular area (the endplate). This chapter will discuss the mechanisms, surgical techniques, outcomes, and complications of aqueous shunt surgery in the setting of neovascular glaucoma. Implant types described in this section include the Molteno, Krupin, Schocket, Baerveldt, Ahmed glaucoma valve, and the Ahmed ClearPath. Additionally, this chapter discusses outcomes of combined retinal treatment and aqueous shunt surgery and secondary treatment options if aqueous shunt failure occurs.
Chapter
Panretinal photocoagulation (PRP) has been a standard of care procedure since the 1970s to manage anterior segment neovascularization associated with ischemic retinal diseases. Since retinal non-perfusion plays a direct role in anterior segment neovascularization, PRP is effective in lowering the angiogenic drive for vascular endothelial growth factor (VEGF) production by destroying the peripheral ischemic retina. Although early prophylactic PRP cannot definitively prevent anterior segment neovascularization in patients with underlying ischemic retinal pathology, PRP is effective in regressing anterior segment neovascularization and significantly reducing the risk of neovascular glaucoma. Combining PRP with anti-VEGF agents stimulates faster regression of anterior segment neovascularization and, in some circumstances, facilitates intraocular pressure control in neovascular glaucoma patients. Due to its safety and long-lasting efficacy, PRP is essential in the management of anterior segment neovascularization.
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Diabetic retinopathy (DR) is among the leading causes of blindness at the global level. A review of studies between 2015 and 2018 found that about 1.7% of the general population with any type of diabetes mellitus suffered from proliferative diabetic retinopathy (PDR). Since the 1960s, panretinal photocoagulation (PRP) has been the mainstay of treatment for PDR. During this period, PRP has been credited with a significant degree of success and a relatively low complication rate. However, the advent of anti-vascular endothelial growth factor (anti-VEGF) therapy with the beginning of the new millennium provided a treatment modality that was noninferior to PRP. A decade-long period of comparisons and debates between these two treatment modalities repeatedly favored anti-VEGF over PRP, as studies demonstrated that the former provided potentially superior outcomes to PRP. The aim of this review is to briefly discuss and compare the relevant studies and evidence supporting these two treatments.
Article
Background Diabetic retinopathy is a principal cause of visual damage and blindness, in which laser treatment offers proven therapy. The progressive degeneration of the retina, secondary to diabetes, is believed to cause postural instability although this is not well documented. The aim of our study was to investigate the effects of diabetic retinopathy on standing posture. Research question Does the different retinal functionality correspond to different specific patterns of movements and muscles recruitment? Methods Postural mechanisms and motor strategies were measured by testing subjects in quiet stance on a force platform with surface electromyography under different optic flow stimulations. Root mean square values of the center of pressure time-varying signals and normalized EMG values were used to estimate the contribution and the interdependence of postural control mechanisms. Results People with diabetic retinopathy, and to a greater extent laser group, were more unstable than healthy subjects. The great amplitude of the body sway observed in the retinopathy group, and especially in the laser group, could be an expression of the difficulty for this population in processing this kind of visual information. Significance The increase in muscle activity indicates that there are musculoskeletal and postural changes in the lower limb musculature with increasing severity of diabetic retinopathy. An impaired retinal function might negatively affect postural control in a way that is dependent on the severity of retinal damage.
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Purpose: We evaluated the correlations between visual deficits and patient-reported symptoms in patients with regressed proliferative diabetic retinopathy (PDR) to determine whether there is a psychophysical basis for vision-related impairments. Methods: Visual acuity, reading acuity, contrast sensitivity, frequency doubling perimetry (FDP), Humphrey field analyzer (HFA), and dark adaptation assessed visual function. The National Eye Institute Vision Function Questionnaire-25 (NEI VFQ-25) and Low Luminance Questionnaire (LLQ) assessed quality of life. Results: We recruited 30 adults who received panretinal photocoagulation (PRP) for PDR and 15 control subjects; 22 diabetic and 11 control participants completed a second evaluation 5 years later. Visual acuity of the worse-seeing eyes tended to correlate better with NEI VFQ-25 and LLQ than did the acuity of the better-seeing eyes. Other vision measures were generally not associated with either questionnaire, especially responses related to driving ability and mental health. Visual acuity only detected subnormal performance in 43% to 45% of patients, while FDP 24-2, HFA 60-4, and LLQ detected abnormal performance in >80% of patients. Conclusions: Poor visual acuity may explain some vision-related impairments in daily function. However, many patients with regressed PDR have normal acuity but reduced visual field and poor quality of life. In these patients, their reported symptoms were not fully explained by visual acuity or any psychophysical tests alone. Translational relevance: Visual acuity is a poor indicator of overall visual function in people with regressed PDR. In clinical settings, visual field tests and patient-reported outcomes may provide more comprehensive assessments of their functional deficits than visual acuity.
Chapter
Retinal degenerative diseases cause relentless, progressive loss of vision through a variety of mechanisms, affecting photoreceptors, retinal pigment epithelial cells, and choroidal and/or retinal perfusion. The most sensitive measures of disease severity depend on the primary cell damaged in each retinal degeneration. Visual function measures provide information about how the patient experiences the world and therefore provide clinically meaningful outcome measures of disease activity. Unfortunately, some of the most commonly used tests of visual function, including visual acuity, are insensitive measures of disease severity or progression, while more sensitive functional tests are often variable in patients with retinal degenerative disease. Advanced imaging technology permits evaluation of retinal structure with cellular-level resolution in some cases and provides sensitive, objective measures that complement visual function tests to enable multimodal assessment of retinal degenerative diseases. This chapter outlines measures of visual function and retinal structure that are commonly used to diagnose patients with retinal degenerative disease and monitor disease severity during disease progression and in response to experimental therapies.
Article
Panretinal photocoagulation (PRP) is a mainstay of therapy for retinal ischemic disease. The procedure involves creating thermal burns in the peripheral retina leading to tissue coagulation, the overall consequence of which is improved retinal oxygenation. While highly effective, there have been concerns historically regarding the anatomic effects and visual complications following PRP, the most common of which include choroidal effusions, exudative retinal detachments, macular edema, visual field deficits, and night vision defects. The occurrence of these complications is closely tied to laser parameters such as increased duration and power and intensive treatment in a single sitting, all of which cause increased dispersion of thermal energy within the retina and choroid. The advent of newer laser delivery systems, such as the multispot pattern laser, has greatly mitigated but not eliminated these issues. The following article reviews the most common complications following PRP treatment, including reported occurrences, inciting factors, and underlying pathophysiology.
Article
For decades, panretinal photocoagulation (PRP) treatment has been the standard treatment of proliferative diabetic retinopathy (PDR). In 2015, the Diabetic Retinopathy Clinical Research Network (DRCR.net) showed that a dosage of 0.5 mg of ranibizumab results in noninferior visual acuity at 2 years compared with PRP and also results in less visual field loss, better visual acuity over the course of 2 years, and fewer vitrectomies.¹ Based on those findings, clinicians can choose antivascular endothelial growth factor (anti-VEGF) or PRP when treating PDR. On behalf of the CLARITY study group, Sivaprasad et al² reported results from a randomized clinical trial of anti-VEGF compared with PRP. Study participants (n = 232) had PDR without diabetic macular edema and a visual acuity of 20/80 or better and were randomly allocated to receive treatment with 2.0-mg aflibercept or PRP. Approximately half of the eligible eyes had previous PRP at least 8 weeks before entering the study, but they had continued active neovascularization. Participants that received aflibercept were given a loading dose of 3 injections at 4-week increments. Starting at week 12, the injections were administered based on a clinician assessing neovascularization by a clinical examination and reviewing color photographs. Throughout 1 year, eyes received a mean (SD) of 4.4 (1.7) injections, meaning an average of 1.4 injections between weeks 12 and 52. Most of the eyes in the trial had a baseline visual acuity that was 20/40 or better (90%) and approximately 25% had high-risk PDR. At 1 year, visual acuity with aflibercept was not only noninferior to PRP at the prespecified noninferiority margin of 5 letters, but was also superior (mean difference, 3.9 letters; 95% CI, 2.3-5.6 letters; P < .001). Fewer participants in the group treated with aflibercept (5%) lost 2 or more lines of vision compared with the group undergoing PRP (15%). Although outcomes were slightly worse for eyes with prior PRP, the treatment differences were similar to the full cohort. No eyes in the study developed endophtalmitis, retinal detachment, iris neovascularization, or neovascular glaucoma. The rates of Antiplatelet Trialists’ Collaboration events were 7% with aflibercept and 4% with PRP (P = .24)
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Background: MAIA microperimetry assesses macular sensitivity to projected point light sources and maps eye movements to assess fixation stability. While microperimetry is gaining prominence as an assessment tool in clinical and research settings, there is no consensus on whether it should be performed before or after pupil dilation. No studies to date have examined the effect of pupil dilation on results. The aim of this project was to elucidate the effect of pupil dilation on microperimetry outcomes. Design: Prospective audit. Participants: Twenty healthy patients from post-operative cataract clinic and ten patients with choroideremia to simulate a disease with peripheral visual field loss. Methods: Subjects underwent 10-2 68 point field testing using the MAIA microperimeter on each eye. Subjects then underwent randomised dilation of one eye and the test was repeated in both eyes. Main outcome measures: We compared changes in threshold sensitivity and fixation stability pre- and post-pupil dilation. The undilated eye was analysed for any learning or fatigue effect caused by test repetition. Results: Dilation produced no significant effect on threshold sensitivity (dilation effect: -0.29 decibels (dB), p = 0.23) or fixation stability in healthy controls or in choroideremia patients (dilation effect: +0.08log bivariate contour ellipse area (BCEA) p = 0.14). There was also no significant learning effect seen in the undilated eye, with no improvement in threshold sensitivity (order of eye testing: +0.03logBCEA, p = 0.71). Conclusions: In the clinical setting patients may be tested for 10 degree microperimetry with or without pupil dilation, as both scenarios yield consistent and interchangeable results.
Article
Purpose: To evaluate costs of panretinal photocoagulation (PRP) vs. intravitreal ranibizumab (IVR) for proliferative diabetic retinopathy (PDR). Design: A Markov-style model of cost-effectiveness and cost utility. Participants: There were no participants. Methods: Based on results from Diabetic Retinopathy Clinical Research (DRCR) Network Protocol S, we performed a Markov-style analysis to generate the total 2-year costs for each treatment arm. The cost per line-year saved and cost utility were calculated based on the estimated life years remaining. Both treatment arms were assumed to result in 9 lines of vision saved in 20% of patients. Medicare reimbursement data were acquired to determine costs, which were then separately calculated for practice settings of a hospital-based facility as the highest end of the cost range and a nonfacility in the same geographic area as the lowest end. Cost parameters for a prototypical patient's life expectancy also were modeled and calculated. Main outcome measures: Inputed cost of therapy, cost per line saved, cost per line-year saved, and cost per quality-adjusted life years (QALY). Results: When PRP was the primary treatment, the 2-year cost in the facility setting was $13 053, with cost per line saved $7252, cost per line-year $240, and cost per QALY $7988. In the nonfacility setting costs were approximately 21% lower. When IVR was the primary treatment, the 2-year cost in the facility setting was $30 328, cost per line saved was $16 849, cost per line-year $575, and cost per QALY $19 150. In the nonfacility setting costs were approximately 15% lower. Extrapolation to lifetime therapy yielded the cost per QALY with PRP treatment of $14 219 to $24 005 and with IVR of $138 852 to $164 360. Cost utility for PRP would be 85% lower than IVR in the facility setting and 90% lower than IVR in the nonfacility setting. Conclusions: PRP compared with IVR as primary treatment for PDR is less expensive over 2 years, but both fall well below the accepted cost per QALY upper limit. However, over an average lifetime, the cost differential between PRP and IVR increases, and IVR therapy may exceed the typical accepted limit of cost per QALY.
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To analyze static visual field sensitivity with topographic models of the hill of vision (HOV), and to characterize several visual function indices derived from the HOV volume. A software application, Visual Field Modeling and Analysis (VFMA), was developed for static perimetry data visualization and analysis. Three-dimensional HOV models were generated for 16 healthy subjects and 82 retinitis pigmentosa patients. Volumetric visual function indices, which are measures of quantity and comparable regardless of perimeter test pattern, were investigated. Cross-validation, reliability, and cross-sectional analyses were performed to assess this methodology and compare the volumetric indices to conventional mean sensitivity and mean deviation. Floor effects were evaluated by computer simulation. Cross-validation yielded an overall R (2) of 0.68 and index of agreement of 0.89, which were consistent among subject groups, indicating good accuracy. Volumetric and conventional indices were comparable in terms of test-retest variability and discriminability among subject groups. Simulated floor effects did not negatively impact the repeatability of any index, but large floor changes altered the discriminability for regional volumetric indices. VFMA is an effective tool for clinical and research analyses of static perimetry data. Topographic models of the HOV aid the visualization of field defects, and topographically derived indices quantify the magnitude and extent of visual field sensitivity. VFMA assists with the interpretation of visual field data from any perimetric device and any test location pattern. Topographic models and volumetric indices are suitable for diagnosis, monitoring of field loss, patient counseling, and endpoints in therapeutic trials.
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To determine the effects of argon green panretinal laser photocoagulation on retinal nerve fibre layer thickness, threshold visual fields, and Estermann full-binocular visual fields over time in diabetic retinopathy. Prospective, pilot clinical study. Time-domain optical coherence tomography (TD-OCT) of the optic nerve head and 24-2 SITA-Fast Humphrey/Estermann visual fields (HVF, EVFs) recorded at baseline, 10 weeks, and 6 months post laser. Quantitative field analysis of central 10 degrees, 24 degrees, and binocular visual fields. A total of 10 eye samples were subjected to uncomplicated multiple-session 100 ms panretinal laser using 2000 burns, 300-microm spot, and mean power of 136 mW (SD+/-39.3). TD-OCT detected and quantified an increase in mean retinal nerve fibre layer thickness at 10 weeks (+8 microm; P<0.05) and progressive thinning at 6 months (-4 microm; P<0.05) compared with baseline. Mean threshold sensitivities, and 10 degrees and 24 degrees HVF improved at both time points in the majority (9 of 10 and 8 of 10) of patients. EVFs showed no significant change with treatment. This pilot study shows that conventional argon laser panretinal photocoagulation may increase the retinal nerve fibre layer thickness in the short term, presumably related to laser-induced axonal injury, with progressive thinning of nerve fibre layer over the long term. The 10 degrees and 24 degrees visual fields improved significantly after laser with no adverse effects on the UK standard driving fields.
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Twenty-one diabetics who had had bilateral retinal panphotocoagulation preserving a visual acuity sufficient to pass the Driver and Vehicle Licensing Centre (DVLC) requirements were assessed with regard to their ability to satisfy the DVLC visual field requirements. Of the 19 patients treated with the laser alone, 17 met the requirements for a licence to drive a private vehicle. The use of the Xenon photocoagulator and large total burn area following laser was found to be associated with an increased risk of DVLC field test failure. Adequate PRP with 200 micron burns appeared to induce neovascular regression and be compatible with passing the DVLC field regulations in many patients. Panphotocoagulation of patients with early proliferative retinopathy using 200 micron burns does not appear to jeopardise a driving licence. Guidelines for laser treatment in diabetic retinopathy aimed at preserving the driving field are presented.
Article
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Laser panretinal photocoagulation (PRP) reduces visual loss in proliferative diabetic retinopathy but decreases peripheral retinal function. The Driver and Vehicle Licensing Centre (DVLC) states that when a patient volunteers that he or she has had photocoagulation, a questionnaire will then be sent to the patient's diabetic physician who can refer the patient for formal field testing. Of 30 patients who had PRP, 15 failed DVLC visual field regulations using the Esterman binocular field test on the Humphrey field analyser. The failures were more likely to have had treatment with a xenon laser, but there was no difference between the groups as regards age, number of burns or whether an argon or diode laser was used. The patients who failed were more likely to be hypertensive (p = 0.04). Two patients with unilateral PRP could not meet the driving regulations because of other field defects. Diabetes itself causes field defects, and therefore even with small amounts of laser, formal field testing may be necessary.
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Although laser panretinal photocoagulation (PRP) for proliferative diabetic retinopathy is known to cause peripheral field constriction, the risks of failing the UK driving field test following treatment are currently unclear as the small number of previous studies have conflicting results. Following PRP using only argon laser with a 500 microns spot size, both uniocular and binocular Esterman visual fields from 60 diabetic patients were assessed by the Chairman of the Visual Standards Sub-Committee of the Royal College of Ophthalmologists. Forty-two per cent of uniocular fields from treated eyes failed. Twelve per cent of binocular fields from those having bilateral PRP failed. Type II diabetes was associated with a significant increase in the risk of failure. Although there is a high risk of failure in any given treated eye, 88% of diabetics will pass a binocular field test, even if both eyes are treated.
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The Pascal is a semiautomated photocoagulator that delivers a pattern array of multiple burns in a rapid predetermined sequence with a single foot pedal depression. Each burn is reduced to 10 or 20 ms to achieve this. The authors report their early experience with this system. 75 procedures done in 60 patients divided into four groups-group A, patients undergoing panretinal photocoagulation (PRP); group B, patients undergoing focal or modified grid macular laser; group C, patients undergoing macular grid and group D, patients undergoing retinopexy-were retrospectively studied. 31/34 procedures in group A, 24/26 procedures in group B, 5/7 procedures in group C and all eight patients in group D had successful outcomes. Significantly higher powers were required with the Pascal than with conventional laser (p<0.001) in eyes that underwent PRP and focal/modified grid macular treatment with both systems. Single session PRP was successfully performed in five patients, and five were successfully treated with a macular grid using pattern arrays only. No adverse events were noted. Although the shorter pulse duration of the Pascal necessitates the use of a higher power, it is not associated with adverse effects. The results here suggest that the Pascal photocoagulator is safe and effective, and offer several potential advantages related to the brief exposure time.
Article
Aims To validate the EyeSuite version of German Adaptive Threshold Estimation (GATE), a new thresholding algorithm for automated static perimetry. Methods Specification of agreement and its clinical evaluation as validation criteria. Comparison of local differential luminance sensitivity (DLS) and test time values between the prototype version of GATE (GATEp) and a clinical trial version, implemented in EyeSuite (GATEe), by means of modified Bland–Altman plots. All examinations were performed on the Octopus 900 perimeter (Haag-Streit Inc., Köniz, Switzerland). Visually impaired patients (anterior ischaemic optic neuropathy [n=3], glaucomatous optic neuropathy [n=15], (post-)chiasmal visual pathway lesion [n=6], retinitis pigmentosa [n=6]) were either tested with grid 30A (30° excentricity, 83 test locations) or grid 84NO (90° excentricity, 109 test locations, patients with RP only). Results The comparison of local DLS values showed good-to-acceptable agreement between GATEp and GATEe (bias <2 dB, limits of agreement [LOA] <5 dB) and very good repeatability for GATEp (bias <0.5 dB, LOA<3 dB). Median test times for GATEp and GATEe were 7.8 and 8.8 min for the 30° grid and 6.7 and 7.8 min for the 90° grid. Conclusions GATEp and GATE, implemented in the commercially available EyeSuite software package (GATEe), show good agreement regarding local differential luminance sensitivity. GATEe can thus be also recommended for clinical practice. Clinical trial number NCT01265628.
Article
Short-pulse neodymium: YAG clinical laser systems permit noninvasive incision of transparent intraocular structures. Selection and safe use of these photodisruptors, however, require a limited understanding of certain basic physical principles. These principles are reviewed and applied in a series of optical experiments designed to study the performance and safety of clinical, short-pulse laser systems. The results of these experiments are presented, in addition to an analysis of current and proposed photodisruptors.
Article
One hundred consecutive patients who underwent bilateral pan-retinal photocoagulation (PRP) for proliferative diabetic retinopathy were assessed in accordance with the UK Driver and Vehicle Licensing Agency (DVLA) guidelines. Visual acuity was documented, and visual fields were assessed using the Esterman test. Among the 30% of patients who failed to reach the visual standards required for a driving licence, three groups were identified: those who failed to attain either the required binocular visual acuity (n = 4), or visual fields (n = 9), or both (n = 17). Previous studies reveal a large variation in DVLA field test failure following PRP treatment for proliferative diabetic retinopathy. Our results show a 19% failure rate solely attributable to treatment, which is at the lower end of previously reported studies (20-80%). The reasons for this discrepancy are discussed. We conclude that modern treatment procedures for proliferative diabetic retinopathy may be undertaken with the knowledge that in the majority of cases a patient's driving licence is unlikely to be revoked.
Article
Incidence data on which to base targets and protocols for screening for sight-threatening diabetic retinopathy are few. We aimed to investigate yearly and cumulative incidence of any retinopathy, maculopathy, and sight-threatening diabetic retinopathy in patients with type 2 diabetes in an established systematic programme and to calculate optimum screening intervals according to retinopathy grade at baseline. We investigated all patients with type 2 diabetes registered with enrolled general practices (except those who were attending an ophthalmologist) who had retinopathy data available at baseline and at least one further screening event. To screen patients, we used non-stereoscopic three-field mydriatic photography and modified Wisconsin grading. Sight-threatening diabetic retinopathy was defined as moderate preproliferative retinopathy or worse, or clinically significant maculopathy in either or both eyes. Results were obtained from 20 570 screening events. Yearly incidence of sight-threatening diabetic retinopathy in patients without retinopathy at baseline was 0.3% (95% CI 0.1-0.5) in the first year, rising to 1.8% (1.2-2.5) in the fifth year; cumulative incidence at 5 years was 3.9% (2.8-5.0). Rates of progression to sight-threatening diabetic retinopathy in year 1 by baseline status were: background 5.0% (3.5-6.5), and mild preproliferative 15% (10.2-19.8). For a 95% probability of remaining free of sight-threatening diabetic retinopathy, mean screening intervals by baseline status were: no retinopathy 5.4 years (95% CI 4.7-6.3), background 1.0 years (0.7-1.3), and mild preproliferative 0.3 years (0.2-0.5). A 3-year screening interval could be safely adopted for patients with no retinopathy, but yearly or more frequent screening is needed for patients with higher grades of retinopathy.
Article
To measure the cumulative incidence of any retinopathy, maculopathy and sight-threatening diabetic retinopathy (STDR), and calculate optimal screening intervals by retinopathy grade at baseline for patients with Type 1 diabetes attending an established systematic retinal screening programme. All patients with Type 1 diabetes registered with enrolled general practitioners, excluding only those attending an ophthalmologist, were studied if retinopathy data was available at baseline and at least one further screen event. Screening utilized non-stereoscopic 3-field mydriatic photography and modified Wisconsin grading. STDR was defined as moderate pre-proliferative retinopathy or greater and/or significant maculopathy in any eye. Patients (n=501) underwent 2742 screen events. Cumulative incidence of STDR in patients without baseline retinopathy was 0.3% (95% CI 0.0-0.9) at 1 year, rising to 3.9% (1.4-5.4) at 5 years. Rates of progression to STDR in patients with background and mild pre-proliferative retinopathy at 1 year were 3.6% (0.5-6.6) and 13.5% (4.2-22.7), respectively. Progression to STDR was greater in patients with a higher grade of baseline retinopathy (P=0.001) or a longer disease duration (P=0.003). For a 95% likelihood of remaining free of STDR, mean screening intervals by baseline status were: no retinopathy 5.7 (95% CI 3.5-7.6) years, background 1.3 (0.4-2.0) years and mild pre-proliferative 0.4 (0-0.8) years. Screening at 2-3 year intervals, rather than annually, for patients without retinopathy in Type 1 diabetes is feasible because of the low risk of progression to STDR, and may result in significant cost savings for a screening programme. Patients with higher grades of retinopathy require screening at least annually or more frequent.
Article
To clarify the evolution of laser scars and factors that possibly affect progression of laser-induced chorioretinal atrophy. The authors quantified 191 areas of laser scarring from panretinal photocoagulation in 19 eyes with diabetic retinopathy and calculated the expansion rate of the laser scars. They also analyzed factors affecting expansion, including location, laser wavelength, and follow-up period. The follow-up period ranged from 36 to 122 months (mean, 62 months). Most (89.5%) laser scars gradually increased in size. The mean annual expansion rates were 12.7% in the posterior pole and 7.0% in the midperiphery. The annual expansion rate (16.5%) more than 4 years (late period) after treatment was higher than that (8.8%) within 4 years of treatment (early period). The expansion rate was minimal (1.2%) after argon laser treatment, whereas it was 11.7% after treatment with a 590-nm wavelength laser and 15.8% after treatment with a 610-nm wavelength laser. Laser photocoagulation causes relentless expansion of laser scars over a long period. Laser scars enlarged more in the posterior pole. Lasers of a longer wavelength contributed to larger areas of chorioretinal atrophy.
Article
The Activity Inventory (AI) is an adaptive visual function questionnaire that consists of 459 Tasks nested under 50 Goals that in turn are nested under three Objectives. Visually impaired patients are asked to rate the importance of each Goal, the difficulty of Goals that have at least some importance, and the difficulty of Tasks that serve Goals that have both some importance and some difficulty. Consequently, each patient responds to an individually tailored set of questions that provides both a functional history and the data needed to estimate the patient's visual ability. The purpose of the present article is to test the hypothesis that all combinations of items in the AI, and by extension all visual function questionnaires, measure the same visual ability variable. The AI was administered to 1880 consecutively-recruited low vision patients before their first visit to the low vision rehabilitation service. Of this group, 407 were also administered two other visual function questionnaires randomly chosen from among the Activities of Daily Living Scale (ADVS), National Eye Institute Visual Functioning Questionnaire (NEI VFQ), 14-item Visual Functioning Index (VF-14), and Visual Activities Questionnaire (VAQ). Rasch analyses were performed on the responses to each VFQ, on all responses to the AI, and on responses to various subsets of items from the AI. The pattern of fit statistics for AI item and person measures suggested that the estimated visual ability variable is not unidimensional. Reading-related and other items requiring high visual resolution had smaller residual errors than expected and mobility-related items had larger residual errors than expected. The pattern of person measure residual errors could not be explained by the disorder diagnosis. When items were grouped into subsets representing four visual function domains (reading, mobility, visual motor, visual information), and separate person measures were estimated for each domain as well as for all items combined, visual ability was observed to be equivalent to the first principal component and accounted for 79% of the variance. However, confirmatory factor analysis showed that visual ability is a composite variable with at least two factors: one upon which mobility loads most heavily and the other upon which reading loads most heavily. These two factors can account for the pattern of residual errors. High product moment and intraclass correlations were observed when comparing different subsets of items within the AI and when comparing different VFQs. Visual ability is a composite variable with two factors; one most heavily influences reading function and the other most heavily influences mobility function. Subsets of items within the AI and different VFQs all measure the same visual ability variable.
The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of Diabetic Retinopathy Study findings
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Initial experience with the Pascal photocoagulator: a pilot study of 75 procedures
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