The British journal of ophthalmology

Published by BMJ Publishing Group
Online ISSN: 1468-2079
Print ISSN: 0007-1161
As the largest terrestrial lens, the atmosphere produces myriad interesting effects, but perhaps none so fabled as the green flash. And yet, for all of its stories, its description is recent. Any society can that can construct structures like the Pyramids or Stonehenge for astronomical purposes must surely have observed the green flash, yet it was not described in writing until 1836 when Captain George Back on the HMS Terror wrote about seeing it while on an expedition to the Arctic ( Meinel, Meinel, Sunsets, Twilights, and Evening Skies , Cambridge: Cambridge University Press, 1983 ). Later, the phenomenon was mythologised when Jules Verne wrote of it in a book entitled Le Rayon Vert . He described a controversial Norse legend regarding the phenomenon which states that anyone who witnesses a green flash will always be true “in matters of the heart.” Little evidence, however, exists that this indeed was a Norse legend. Nevertheless, the green flash is legendary and many suspect that it does not actually exist, that it is an afterimage. This suspicion is belied by the two images on the cover showing different aspects of the same phenomenon. A camera cannot record an afterimage, and furthermore, the phenomenon has also been witnessed at dawn …
The belief that the tear film is aqueous based and the ocular surface changes seen in Sjogren’s syndrome are due to desiccation, cause eye care practitioners to water the dry eye. Studies show the tear film is dominated by mucin and not water.1 2 It is not a 7–10 μm thin film, but a 30–35 μm thick mucin gel. Bicarbonate may be critical to forming this gel as it is in forming the bicarbonate mucin gel that protects the stomach from autodigestion.3 The hallmark of the aqueous deficient dry eye, rose bengal staining of the conjunctiva, is not produced by desiccated cells, but is due to a deficiency in the protective mucin gel.4 The first major innovation in the treatment of the dry eye seen in Sjogren’s syndrome was the introduction of preservative-free artificial tears. Although the absence of preservatives allowed frequent topical application, the improvement seen in these severe dry eyes was more the result of the elimination of toxic preservatives …
Mean intraocular pressure (IOP) readings (with the standard deviation) during 24 h monitoring; bimatoprost monotherapy (IOP 1) compared with bimatoprost/dorzolamide therapy (IOP 2). 
Characteristics of the patients
The mean intraocular pressure, blood pressure, ocular perfusion pressure and heart rate on bimatoprost and bimatoprost+dorzolamide treatment
Ophthalmic artery haemodynamics by colour Doppler imaging
Central retinal artery haemodynamics by colour Doppler imaging Bimatoprost Bimatoprost+ dorzolamide
To assess the additive effect of dorzolamide hydrochloride 2% on the diurnal intraocular pressure (IOP) curve and retrobulbar haemodynamics in patients with primary open-angle glaucoma (POAG) treated with morning-dosed bimatoprost 0.03%. Twenty-five patients with POAG were evaluated in a prospective, single-masked study. After a 1 week run-in period with bimatoprost all patients were treated with bimatoprost dosed once in the morning for 1 month, after which dorzolamide was added twice daily for 2 months. Goldmann applanation IOP, arterial blood pressure (ABP) and heart rate were measured every 2 h for 24 h and diurnal ocular perfusion pressure (OPP) was calculated. Colour Doppler imaging (CDI) of the ophthalmic artery (OA) and the central retinal artery (CRA) was recorded five times daily. All measurements were taken after the two phases of treatment and were compared. The mean baseline IOP was 14.8 ± 3.5 mm Hg. Mean IOP following bimatoprost monotherapy (12.8 ± 2.9 mm Hg) and after 2 months of dorzolamide adjunctive therapy (12.2 ± 2.6 mm Hg) were not statistically significantly different (p=0.544). Only at the 4:00 h time point was IOP significantly reduced using the bimatoprost/dorzolamide combined treatment (p=0.013). The 24 h IOP fluctuations were lower when dorzolamide was added (6.0 ± 2.3 mm Hg vs 4.6 ± 1.5 Hg, p=0.0016). Repeated analysis of variance detected a significant decrease of vascular resistance in the OA (p=0.0167) with adjunctive dorzolamide treatment. The addition of dorzolamide to morning-dosed bimatoprost had an additive hypotensive effect only on the night-time IOP curve at 4:00 h and resulted in a lower IOP fluctuation. Dorzolamide added to bimatoprost may reduce vascular resistance in the OA.
To compare the intraocular pressure (IOP) reducing effect of latanoprost 0.005% and 0.001%. Twenty four patients with glaucoma or ocular hypertension were randomised into two groups. Twelve patients (group 1) were given latanoprost 0.005% once daily for 4 weeks and then latanoprost 0.001% once daily for the following 4 weeks. Twelve patients (group 2) were given latanoprost 0.001% once daily for 4 weeks and then latanoprost 0.005% for the following 4 weeks. There was a significant IOP reduction from baseline in both groups on day 28 as well as on day 56. When the results from both groups were used for calculations, the mean IOP reduction from baseline after 4 weeks of treatment with latanoprost 0.005% (day 28 or 56) was 9.6 (SD 3.3) mm Hg (35.0%). After 4 weeks of treatment with latanoprost 0.001%, the IOP reduction (day 28 or 56) was 7.6 (3.4) mm Hg (27.7%). The difference in IOP reduction between the two concentrations was 2.0 (2.3) mm Hg (p < 0.001). Latanoprost 0.005% was more effective than latanoprost 0.001% in reducing IOP. Even the lower concentration was surprisingly effective, and potentially may be of importance for use in clinical practice. Furthermore, it is at present unknown whether the increase in iris pigmentation seen in certain patients treated with latanoprost 0.005% is dose dependent and might be less pronounced with latanoprost 0.001%. Long term studies with a larger number of patients are required in order to answer this question.
Patient demographics 
To evaluate the efficacies of bimatoprost and travoprost for lowering of intraocular pressure (IOP) for the treatment of glaucoma and ocular hypertension. Prospective, randomised, investigator-blinded, parallel-group clinical trial. After completing a washout of all glaucoma drugs, patients (n = 157) were randomised to bimatoprost or travoprost for 6 months. Visits were at baseline, 1 week, and 1, 3 and 6 months. IOP was measured at 09:00 h at each visit and also at 13:00 and 16:00 h at baseline and at 3 and 6 months. No significant between-group differences were observed in IOP at baseline, at 09:00, 13:00 or 16:00 h (p> or =0.741). After 6 months, both drugs significantly reduced IOP at every time point (p< or =0.001). After 6 months, mean IOP reduction at 09:00 h was 7.1 mm Hg (27.9%) with bimatoprost (n = 76) and 5.7 mm Hg (23.3%) with travoprost (n = 81; p = 0.014). At 13:00 h, mean IOP reduction was 5.9 mm Hg with bimatoprost (25.3%) and 5.2 mm Hg (22.4%) with travoprost (p = 0.213). At 16:00 h, the mean IOP reduction was 5.3 mm Hg (22.5%) with bimatoprost and 4.5 mm Hg (18.9%; p = 0.207) with travoprost. Both study drugs were well tolerated, with ocular redness the most commonly reported adverse event in both treatment groups. Bimatoprost provided greater mean IOP reductions than travoprost.
The efficacy of bimatoprost and travoprost in patients with glaucoma and ocular hypertension Dr Cantor’s article1 ( see page 1370 )on the efficacy of bimatoprost and travoprost in patients with glaucoma and ocular hypertension shows again that both these drugs are efficacious in lowering intraocular pressure (IOP). The study is a prospective, randomised investigator-blinded trial, which has results similar to those found in studies carried out with the drugs in this class. Dr Cantor found that bimatoprost lowered IOP slightly more than travoprost in this study population. This is the first relatively large two-arm study to show this in a head-to-head design. The current study supports others who have shown that bimatoprost is somewhat more efficacious than travoprost. What is reassuring about this study is that there are no surprises, and the results appear to be consistent with what has been seen in the collection of other studies comparing drugs in this class. The relative degrees of IOP reduction, rates of hyperaemia and clinical success parameters are within the range …
To determine the effect of brimonidine tartrate 0.2% and latanoprost 0.005% on pulsatile ocular blood flow (POBF) in patients with normal tension glaucoma (NTG). NTG patients with progressive optic neuropathy, new disc haemorrhage, or field defects that threatened fixation were enrolled into a randomised, investigator masked, crossover study. Group I patients received 4 weeks each of latanoprost, lubricant, and brimonidine, while group II patients received 4 weeks each of brimonidine, lubricant, and latanoprost. Diurnal POBF was measured at baseline and after each 4 week treatment. 25 patients completed the study and had reliable POBF measurement at each visit. There was no significant diurnal change in baseline POBF (p = 0.768). Latanoprost increased POBF by 213 (SD 257) micro l/min (22.8%, p <0.001) while brimonidine increased it by 97 (183) micro l/min (10.4%, p = 0.014). POBF increased at 8 am (p = 0.004), 12 noon (p = 0.002), and 4 pm (p <0.001) with latanoprost, while it increased only at 8 am (p = 0.016) with brimonidine. After adjusting for the factor of IOP, neither latanoprost nor brimonidine increased POBF significantly. Latanoprost increases the mean POBF that is related to its IOP lowering effect. The increase in POBF noted after brimonidine is within the range of long term variation and may not be attributable to the drug effect.
Proportion of subjects with intraocular pressure (IOP) ≤18 mm Hg at follow-up visits (intent-to-treat population). *p<0.05 versus latanoprost. LBN, latanoprostene bunod.
Mean diurnal intraocular pressure (IOP) in the study eye at baseline and on Day 28 (intent-to-treat population). *p=0.005 versus latanoprost; †p=0.009 versus latanoprost. LBN, latanoprostene bunod.
To assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension. Randomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28. Of the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%-0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments. LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated. NCT01223378. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
To evaluate efficacy and safety in patients with ocular hypertension or open angle glaucoma changed to latanoprost/timolol fixed combination (LTFC). A prospective, multicentre, historical control in which qualified patients had their previous therapy substituted by LTFC and were followed for at least 2 months. In 1676 patients LTFC was continued in 93% throughout the observation period. In all patients LTFC reduced the intraocular pressure (IOP) from 20.6 (SD 3.8) to 17.7 (3.0) mm Hg (p<0.001) compared to previous monotherapies including latanoprost, timolol, alpha agonists or carbonic anhydrase inhibitors (CAI). LTFC provided more efficacy after changing from adjunctive therapies including: a beta blocker added to either CAI, alpha agonist, or pilocarpine, or CAI added to an alpha agonist, or latanoprost added to either CAI, alpha agonist, or beta blocker (unfixed combination), and travoprost added to timolol (p<0.007). LTFC was as effective as latanoprost used with dorzolamide/timolol fixed combination (-0.9 mm Hg, p = 0.1792). The most common reason to discontinue therapy was lack of efficacy (n = 70, 4%) and adverse event (n = 17, 1%). In a clinical setting, patients who have their monotherapy or adjunctive therapy substituted with LTFC may experience reduced IOP, good tolerability, and continuation of therapy for the first 2-3 months of treatment.
To compare the long-term outcomes of primary pterygium surgery with combined conjunctival rotational autograft and mitomycin C (CRA-MMC), mitomycin C alone (MMC) and limbal conjunctival autograft (LCAU). The outcomes of primary pterygium excision followed by conjunctival rotational autograft (CRA) combined with intraoperative 0.02% MMC for 5 min (group 1, CRA-MMC, n=61) were compared with historical control groups consisting of, pterygium excision with MMC (group 2, n=47), and, pterygium excision with limbal conjunctival autograft (LCAU) (group 3, n=29). The main outcome measures were recurrence rate and complications. The mean follow-up period was 101±3 months, 138±2 and 137±2 months in the CRA-MMC, MMC and LCAU groups respectively. Recurrence was noted in one patient (1.6%) in the CRA-MMC, 12 patients with MMC (25.5%) and 2 patients with LCAU (6.9%). The difference in recurrence rate between CRA-MMC and MMC was statistically significant (p<0.001). Early postoperative complications included 3 conjunctival cysts (1 from the CRA-MMC, 2 with MMC alone), 2 symblephara (1 in the MMC group, 1 in the LCAU group), and 1 granuloma in the CRA-MMC group. Pterygium excision followed by CRA-MMC or LCAU are effective means of preventing recurrence. The use of CRA-MMC in pterygium excision may be considered for cases where conventional autograft harvesting is contraindicated or when large grafts for double-head pterygium are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
The effectiveness of instillation of mitomycin C eyedrops on the recurrence rate of pterygium was assessed in patients undergoing primary pterygium surgery. Any side effects were also noted. Primary pterygia in 38 consecutive patients were surgically excised during July to December 1992. After surgery, mitomycin C 0.02% eyedrops twice daily for 5 days as well as dexamethasone 0.1% four times tapered for the next 6 weeks were instilled. Postoperative follow up ranged from 6 to 11 months. In one patient the pterygium recurred after 3 months (recurrence rate 2.6%). The side effects encountered were: avascularised sclera in 13 cases between 1-10 months postoperatively; ocular discomfort and lacrimation in five cases; superficial punctate keratitis during the first month in three cases; pyogenic granuloma in two cases. In one patient steroid induced increased intraocular pressure was found 4 weeks after surgery. The adverse side effects were all mild, self limiting, and easily treated. This study suggests that postoperative instillation of mitomycin C 0.02% eyedrops twice daily for 5 days following excision of primary pterygium is an effective and safe treatment to obviate pterygium recurrence.
Mitomycin C (MMC) and limbal conjunctival autograft (LCAU) are two known useful adjuvants in the prevention of pterygial recurrence. This study was conducted to compare the outcome of these two treatments. Prospective study on consecutive cases of primary pterygium (February 2001 to March 2002) randomised into two adjuvant groups: (1) intraoperative 0.02% MMC for 5 minutes or (2) LCAU. Patients were followed for recurrence (defined as fibrovascular tissue invading the cornea >1.5mm) and complications for a period of one year. 115 eyes in 114 patients who completed the study were randomised to receive MMC (n = 63) and LCAU (n = 52). There were 10 recurrences (15.9%) in the MMC group and only one recurrence (1.9%) in the LCAU group. There was a statistically significant difference in the recurrence rate between the two groups (p = 0.04). There were a total of three conjunctival cysts, three symblephara, one granuloma, and one dellen. No other visually significant complications were encountered in either group. Although LCAU resulted in better one year success rates, it is technically more difficult and inapplicable in cases with previous limbal disturbance. Simple excision followed by MMC or LCAU are both safe and acceptable adjuvants for pterygium excision. Choice of adjuvant should be carefully made based on assessment of recurrence risk, local practices, and surgeon's expertise.
To compare the conjunctival and corneal reactions of commercially available solution of latanoprost (Xalatan) and preservative-free (PF) tafluprost in rabbits. The rabbits received 50 microl of phosphate-buffered saline (PBS), PF-tafluprost 0.0015%, latanoprost 0.005% or benzalkonium chloride (BAK) 0.02%; all solutions were applied at 5 min intervals for a total of 15 times. The ocular surface toxicity was investigated using slit-lamp biomicroscopy examination, flow cytometry (FCM) and on imprints for CD45 and tumour necrosis factor-receptor 1 (TNFR1) conjunctival impression cytology (CIC) and corneal in vivo confocal microscopy (IVCM). Standard immunohistology also assessed inflammatory/apoptotic cells. Clinical observation and IVCM images showed the highest ocular surface toxicity with latanoprost and BAK, while PF-tafluprost and PBS eyes presented almost normal corneoconjunctival aspects. FCM showed a higher expression of CD45+ and TNFR1+ in latanoprost- or BAK-instilled groups, compared with PF-tafluprost and PBS groups. Latanoprost induced fewer positive cells for inflammatory marker expressions in CIC specimens compared with BAK-alone, both of which were higher than with PF-tafluprost or PBS. Immunohistology showed the same tendency of toxic ranking. The authors confirm that rabbit corneoconjunctival surfaces presented a better tolerance when treated with PF-tafluprost compared with commercially available latanoprost or BAK solution.
Patients data 
Rejection data 
Mean IOP (mm Hg ±SD) 
ABO compatibility 
The present study aims to identify the rate of rejection and safety of 0.03% tacrolimus eye drops associated with 1% prednisolone in a topical formulation, comparing them with the use of 1% prednisolone eye drops alone in patients with high-risk corneal transplantation. Retrospective cohort study with 72 patients (72 eyes) who underwent more than one penetrating keratoplasty (PK) in the same eye or had severe chemical burn between 2004 and 2011 in the department of cornea and external disease of the Clinical Hospital of Porto Alegre, Brazil. We compared the records of 36 patients that performed unilateral PK and received only 1% prednisolone eye drops between May 2004 and July 2008, with 36 patients that received 0.03% tacrolimus eye drops in addition to 1% prednisolone between August 2008 and August 2011. The mean follow-up of the group exposed to tacrolimus was 23.1 months and 24.0 in the prednisolone alone group. The demographics, intraoperative and initial indications for first PK were similar between groups, as well as the number of regrafts performed. Intraocular pressure (IOP) was not statistically different among groups. Regarding irreversible rejections, topical tacrolimus showed greater protection: only seven grafts (19.4%) lost transparency against 16 (44.4%) in the 1% prednisolone alone group (p <0.05). Topical 0.03% tacrolimus was effective in preventing irreversible rejection in patients with high-risk corneal transplantation without increasing IOP.
Ophthalmic manifestations of vernal keratoconjunctivitis (VKC) may be divided into actual allergic responses (giant papillae, Trantas dots) and sequelae of chronic inflammation (tarsal cicatrisation, corneal vascularisation). Mast cell-targeted therapy and anti-histamines are useful in alleviating symptoms from early pathogenic steps,1 but once T-cell-mediated reactions enter stage, these may become insufficient. A vicious cycle develops when chronic ocular surface inflammation results in tarsal scarring, secondary dry eyes and eyelid malposition. Topical steroid is indicated for severe exacerbations, but its long-term use is associated with complications such as cataract and glaucoma. Topical cyclosporine is the only commercially available in 0.05% and is indicated for aqueous deficient dry eyes. However, a previous report has shown that vernal ulcers would not respond to concentrations <1%.2 Tacrolimus is more …
Mean (±SD) worse eye IOP at each time point through 12 weeks of study in the per-protocol population. IOP, intraocular pressure; PF, preservative-free.
Treatment differences (bimatoprost/timolol PF−bimatoprost/timolol) at each time point in average eye IOP (intent-to-treat population). Missing values were imputed using the last observation carried forward method. IOP, intraocular pressure; PF, preservative-free.
Treatment differences (bimatoprost/timolol PF−bimatoprost/timolol) at each time point in change from baseline worse eye IOP in the per-protocol population. IOP, intraocular pressure; PF, preservative-free. Adapted from Day et al.14
To compare the efficacy and safety of single-dose bimatoprost 0.03%/timolol 0.5% preservative-free (PF) ophthalmic solution with bimatoprost 0.03%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. In this multicentre, randomised, parallel-group study, patients were randomised to bimatoprost/timolol PF or bimatoprost/timolol once daily in the morning for 12 weeks. Primary efficacy endpoints, reflecting differing regional regulatory requirements, included change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12, and the average eye IOP at weeks 2, 6 and 12 in the intent-to-treat population. 561 patients were randomised (278 to bimatoprost/timolol PF; 283 to bimatoprost/timolol); 96.3% completed the study. Both treatment groups showed statistically and clinically significant mean decreases from baseline in worse eye IOP and in average eye IOP at all follow-up time points (p<0.001). Bimatoprost/timolol PF met all pre-established criteria for non-inferiority and equivalence to bimatoprost/timolol. Ocular adverse events were similar between treatment groups, with conjunctival hyperaemia being the most frequent. Most were mild or moderate in severity. Bimatoprost/timolol PF demonstrated non-inferiority and equivalence in IOP lowering compared with bimatoprost/timolol, with no significant differences in safety and tolerability. NCT01177098.
Demographics and baseline characteristics, intent-to-treat population
Mean±SD change from baseline in worse eye intraocular pressure (mm Hg), per-protocol population
Patients with ocular adverse events ≥2% in either group, safety population
Mean average intraocular pressure (IOP) at each time point, intent-to-treat population. Difference between groups <0.3 mm Hg. Note the lines overlay making them somewhat indistinguishable. BIM, bimatoprost 0.03% ophthalmic solution (blue); BIM PF, bimatoprost 0.03% preservative-free ophthalmic solution (red).
Between-group differences at each time point in change from baseline in worse eye intraocular pressure (IOP), per-protocol population. Upper limit of 95% CI of between-group difference ≤0.75 mm Hg at week 12.
Background/Aim To evaluate efficacy and safety of bimatoprost 0.03% preservative-free (PF) ophthalmic solution versus bimatoprost 0.03% (Lumigan) ophthalmic solution for glaucoma or ocular hypertension. Methods In this double-masked, parallel-group study, patients were randomised to bimatoprost PF or bimatoprost for 12 weeks. The primary analysis for non-inferiority was change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12. For equivalence, it was average eye IOP in the intent-to-treat population at each time point at weeks 2, 6 and 12. Results 597 patients were randomised (bimatoprost PF, n=302 and bimatoprost, n=295). The 95% CI upper limit for worse eye IOP change from baseline was <1.5 mm Hg at each week 12 time point, meeting prespecified non-inferiority criteria. The 95% CI upper limit for the treatment difference for average IOP was 0.69 mm Hg and the lower limit was −0.50 mm Hg at all follow-up time points (hours 0, 2 and 8 at weeks 2, 6 and 12), meeting equivalence criteria. Both treatments showed decreases in mean average eye IOP at all follow-up time points (p<0.001), were safe and well tolerated. Conclusions Bimatoprost PF is non-inferior and equivalent to bimatoprost in its ability to reduce IOP-lowering with a safety profile similar to bimatoprost.
To evaluate the efficacy of combined treatment with commercially available 0.05% topical ciclosporin and topical corticosteroid compared with treatment with topical corticosteroids only after high-risk keratoplasty. Patients and methods: A total of 47 high-risk keratoplasties were randomly divided into two groups based on the postoperative immunosuppression. Twenty-five eyes (group 1) were treated with 0.05% ciclosporin and dexamethasone 0.1%, and 22 eyes (group 2) were treated with dexamethasone only. The clinical outcome of penetrating keratoplasty was evaluated by the rate of rejection-free graft survival and graft survival evaluation by the Kaplan-Meier logrank test. The average length of follow-up was 20.2 (SD 7.1) months in group 1 and 18.5 (6.6) months in group 2 (p = 0.421). Rejection-free graft survival rates were 60.8% in group 1 and 54.5% in group 2 (Kaplan-Meier logrank test, p = 0.474). In group 1, the graft survival rate was 73.9%; in group 2, the graft survival rate was 68.1%. The difference in the graft survival rates between the groups was also not statistically significant (Kaplan-Meier logrank test, p = 0.518). In high-risk corneal grafts, the efficacy of 0.05 percent commercially available topical ciclosporin combined with dexamethasone topically was not better than that of dexamethasone alone in preventing rejection.
A double masked randomised trial comparing 0.05% mequitazine eye drops with 0.05% levocabastine and placebo was carried out in otherwise healthy volunteers allergic to house dust mites (Dermatophagoides pteronyssinus). Double masked, randomised, single centre study, comparing three parallel treatment groups. 60 healthy adults with a confirmed history of allergic conjunctivitis to house dust mites for at least 2 years were included and completed the trial. Conjunctival provocation tests (CPT) were done at screening, at visit 2 (V2) (1 week later), and at visit 3 (V3) (2 weeks after V2). Treatment was instilled in the same eye, 5 minutes after the CPT at V2, and twice daily until V3. CPT were scored 5, 10, 15, and 60 minutes after instillation of the dose of Dermatophagoides pteronyssinus antigen determined at inclusion (V2, curative test) or resulting in positivity (V3, preventive test) In the V2 (curative) test the difference between the active treatments and placebo on the redness+itching scores was not significant. At the V3 (preventive) CPT there was a lower number of reactions at the threshold dose with mequitazine (20%) compared to placebo (60%, p = 0.01) or levocabastine (45%, p = 0.10). This trial failed to clearly demonstrate curative superiority of topical antihistamines with placebo, when a single dose of treatment was instilled following CPT. However mequitazine 0.05% eye drops were superior to placebo in preventing a reaction to CPT, after 2 weeks of treatment.
Change from baseline in total symptom and sign scores during the 6-month study period (n=1436 patients). Error bars represent 1 SD. The statistical significance of each score change was evaluated using the Wilcoxon signed rank test.
Distribution of giant papillae (A) and corneal involvement (B) scores. The statistical significance of each score change from baseline was evaluated using the Wilcoxon signed rank test.
Changes from baseline in total sign and symptom scores in patients who did not respond well to prior cyclosporine ophthalmic solution therapy. Error bars represent 1 SD. The statistical significance of each score change was evaluated using the Wilcoxon signed rank test.
Proportions of patients using topical steroids at baseline and throughout the 6-month period during which the patients received topical tacrolimus eye drops.
The objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement. This prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during the study period. Ten clinical signs and six clinical symptoms were rated on a four-grade scale. The primary endpoint was the change from baseline in total clinical signs and symptoms score at the last observation or following 6 months of treatment. Total signs and symptoms score significantly decreased after 1 month of treatment (p<0.001). Giant papillae and corneal lesions were also reduced by tacrolimus eye drop use (p<0.001). The drug proved effective in patients whose condition did not respond well to topical cyclosporine therapy. About 50% of all patients using topical steroids were weaned. The most common adverse reaction was a transient burning sensation (3.20%). Tacrolimus eye drops are highly effective in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement, and may reduce or replace topical steroid use. UMIN 000008640.
The intraocular pressure effect of fluorometholone 0.1% was compared with that of dexamethasone 0.1% by performing corticosteroid provocative tests on 24 matched pairs of eyes. Fifteen of the 24 dexamethasone treated eyes, 62.5%, showed a change in intraocular pressure greater than 5 mmHg, with mean delta P = 8.58 mmHg and range 0 to +20 mmHg. Only 2 of the 24 fluorometholone treated eyes, 8.3%, showed a change in pressure greater than 5 mmHg, with mean delta P = 2.96 mmHg and range -2 to +14 mmHg. There was a highly statistically significant difference between the intraocular pressure effects of topical dexamethasone and fluorometholone (correlated t test, p less than 0.001). Fluorometholone would appear to be the topical steroid of choice for patients with glaucoma and other known steroid responders when topical steroid treatment is indicated.
To evaluate the analgesic effect of topical sodium diclofenac 0.1% during retinal laser photocoagulation. 87 patients, 45 with proliferative diabetic retinopathy treated with two sessions of panretinal photocoagulation (group A), and 42 patients with non-proliferative diabetic retinopathy who underwent grid treatment of the posterior pole (19 bilaterally) (group B). Sodium diclofenac 0.1% or sodium chloride 0.9% drops were topically applied 30-135 minutes before laser treatment in a masked fashion. Patients who had two sessions were given the alternate drug in the second one. Pain level was evaluated immediately after laser treatment with the visual analogue scale (VAS). The results were statistically analysed. Patients in group A reported pain in 85/90 sessions (94%). The average pain level was 44.2% with sodium diclofenac 0.1% drops and 53.1% with sodium chloride 0.9% drops (p = 0.011 by paired t test). Patients in group B reported pain in only 16/60 sessions (26. 7%), and the pain level ranged from 10% to 60% regardless of the kind of drops used. There was no correlation in either group between level of pain and time interval from application of the drops to laser treatment (30-135 minutes) or average energy level used (100-500 mW). Sodium diclofenac 0.1% is useful for pain reduction and should be applied before panretinal photocoagulation.
Percentage of eyes with a change in central sub fi eld retinal thickness at 4 weeks compared with the preoperative examination by treatment group (G1=placebo; G2=ketorolac and G3=nepafenac). 
Preoperative and 30 days postoperative data
Percentage of patients in whom we de fi ned macular oedema using an upper cut-off of two SDs above the mean baseline central sub fi eld thickness (CST) by treatment group (G1=placebo; G2=ketorolac and G3=nepafenac). 
Between-group comparison of central foveal thickness (CFT, μm) measured with SD-OCT
Percentage of patients in whom we de fi ned macular oedema using an upper cut-off of three SDs above the mean baseline central sub fi eld thickness (CST) by treatment group (G1=placebo, G2=ketorolac, and G3=nepafenac). 
Purpose To compare the anti-inflammatory efficacy of ketorolac of tromethamine 0.4% and nepafenac 0.1% eye drops for prophylaxis of cystoid macular oedema (CME) after small-incision cataract extraction. Methods Patients were assigned randomly to three groups. Group 1 patients received a topical artificial tear substitute (placebo); group 2 received ketorolac tromethamine 0.4% (Acular LS, Allergan) and group 3 received nepafenac 0.1% (Nevanac, Alcon). The incidence and severity of CME were evaluated by retinal foveal thickness on optical coherence tomography (OCT) after 1, 4 and 12 weeks. Results One hundred and twenty-six eyes of 126 patients were included in this study. The between-group differences in visual outcomes, central corneal thickness and endothelial cell density were not statistically significant. In all retinal thickness measurements, an increase was detected starting from the postoperative first week until 12 weeks. There was no statistically significant difference between the three groups in any measurement performed by spectral-domain OCT. Conclusions Used prophylactically after uneventful cataract surgery, non-steroidal anti-inflammatory drugs were not efficacious in preventing macular oedema compared with placebo. Trial registration number ClinicalTrials: NCT02084576.
Mean IOP values (mm Hg) during the study (PP population) 
This comparative, open design, phase III study was to assess the non-inferiority of the non-preserved T-Gel 0.1% single dose unit (SDU) versus its preserved multidose (MD) reference. 175 patients with bilateral POAG or OHT were randomised: 87 patients were to receive one drop daily of T-Gel 0.1% MD and 88 patients were to receive one drop daily of T-Gel 0.1% SDU, for a treatment period of 12 weeks. The primary efficacy variable was the change in intraocular pressure (IOP) in the worse eye between the baseline and the last assessment. Subjective and objective ocular signs as well as adverse events were recorded for safety. Global tolerance was assessed by the investigator and by the patient. The mean percentage reduction from baseline IOP was 24% for both treatments groups, which was consistent with previous studies. The safety results were comparable in both treatment groups. Because of gel formulation, mild short lasting episodes of blurred vision occurred for about 20% of patients. The global tolerance assessment reported that both treatments were well tolerated. The overall study results demonstrated that T-Gel 0.1% SDU is not inferior to T-Gel 0.1% MD.
Hyaluronan (sodium hyaluronate) has been shown to confer objective and subjective improvement in patients with dry eye syndrome. This study compared the efficacy and safety of a 0.1% solution of hyaluronan with 0.9% saline, when administered topically to the eye, in the treatment of symptoms of severe dry eye syndrome. A randomised, double blind, crossover clinical trial in which subjects were randomised to receive either hyaluronan or saline, applied as one or two drops to the eye, three or four times a day or as required. After 28 days' treatment, subjects crossed over to the other study medication for a further 28 days' treatment. 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer's score (p=0.0006) and rose bengal staining score (p=0.0001) were observed during treatment with hyaluronan. In a subjective assessment of the effectiveness of two treatments, a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness (p<0.001). No adverse events attributable to hyaluronan treatment were reported. The study demonstrates a clear benefit of hyaluronan over saline, in both subjective and objective assessments of dry eye syndrome. Hyaluronan was shown to be well tolerated.
EVects of treatment on the change of conjunctival surface temperature (°C) 
To compare the efficacy of topical nedocromil 2% with fluorometholone 0.1% in vernal keratoconjunctivitis (VKC). In a double masked random design, 24 patients with severe vernal keratoconjunctivitis were placed at random on nedocromil 2% eye drops in one eye and fluorometholone 0.1% in the fellow eye. At the end of the 2 week treatment period, the patient crossed over the eye drops (if asymptomatic in one eye), or continued with nedocromil sodium in both eyes (if asymptomatic in both eyes). All patients were examined weekly and ocular surface temperature recorded for a period of 6 weeks. Improvement in the watering, discharge, conjunctival hyperaemia, papillary hypertrophy, and Trantas' dots was noted in both groups, but overall fluorometholone was significantly more effective than nedocromil. Eyes treated with fluorometholone showed a significant decrease in ocular surface temperature compared with nedocromil treated eyes (p = 0.03). Both nedocromil and fluorometholone were effective in ameliorating the signs and symptoms of vernal keratoconjunctivitis. No adverse effects were noted in the nedocromil group.
The results of this single-blind randomised trial comparing adrenaline 1% with dipivalyl epinephrine (Propine) 0.1% confirm that both have a significant effect in lowering the intraocular pressure in patients with open-angle glaucoma and ocular hypertension, but it is generally insufficient to warrant their use as the first line medical treatment of these two conditions. There was no significant difference between the intraocular lowering effect of the two preparations, and 60% of patients receiving Propine and 66% of those receiving adrenaline noted side effects.
Demographic profile of the subjects 
Changes in corneal epithelial area, barrier function, and tear function tests 
Changes in corneal epithelial area, barrier function, and tear function tests in eyes with diabetes mellitus and dry eye 
To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion. 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment. Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group. While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.
To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects. In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period after a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (IOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period. The baseline diurnal IOP was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolamide. The trough IOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal IOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p = 0.46). Dorzolamide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events. This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide.
The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis. Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial. 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment. Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.
A trial of the efficacy of low-concentration nonmiotic therapy was carried out, the aim being to minimise the side effects produced by 1% adrenaline or pilocarpine. A total of 77 eyes with open-angle glaucoma were studied in both parts of the trial. Thirty-nine eyes had a base-line pressure of over 28 mmHg and 28 eyes a pressure of 30 mmHg or over. In the comparison between Ganda 1.02 and adrenaline 1% (Simplene) the mean lowering of intraocular pressure was 8.6 mmHg with Ganda and 7.69 mmHg with Simplene. In the comparison between Ganda 1.02 and pilocarpine 1% (Sno-Pilo) the mean decrease was 6.34 mmHg with Ganda and 6.13 mmHg with Sno-Pilo. The resulting falls in intraocular pressure were highly significant statistically, but the differences between the effects of the 3 drugs were not significant. No significant side effects were reported with Ganda 1.02, and in particular no ptosis or superficial punctate staining of the cornea was noted.
A blind randomised cross-over study was conducted on 10 patients (20 eyes) to compare the effect in patients with open-angle glaucoma of metipranolol 0.3% with that of timolol 0.25% on intraocular pressure following one month's topical instillation with each preparation alone. There was no statistically significant difference in intraocular pressure reduction between these two preparations, and the ocular tolerance of both was good. There was no significant difference in the blood pressure, pulse, or pupil diameters of patients receiving either preparation.
The intraocular pressure lowering effect in 30 patients with raised intraocular pressure and open angles following a single application in a randomised double-masked fashion of four concentrations of D-timolol (0.25%, 0.5%, 1.0%, and 2.0%), 0.25% L-timolol, and placebo are presented. The percentage reduction in intraocular pressure after four hours following single-drop instillation range from 20% to 25% in the D-timolol group, 32% in the L-timolol group, and only 8% in the placebo group of treated eyes.
The results of a 12-month blind randomised trial comparing the intraocular pressure lowering effect of timolol 0.25% with timolol 0.5% are presented. 27% of patients (22% of eyes) required additional antiglaucoma medication after a minimum time interval of 6 months to maintain an intraocular pressure less than 23 mmHg. The mean reduction in intraocular pressure (from pretreatment values) at 12 months was 24% for eyes treated with timolol 0.25% and 19% for eyes treated with timolol 0.5%. When reductions in intraocular pressure at each follow-up interval were statistically significant (timolol 0.25% treated eyes compared with timolol 0.5% treated eyes), the significance always favoured timolol 0.25%.
Age specific prevalence rates of myopia (either eye) by different spherical equivalent (SE) cut-off points of all Chinese children in the SCORM study (n = 1467) 
Recent studies of myopia prevalence among children
To determine the association of spherical equivalent (SE) with low uncorrected visual acuity (VA) along with a proposed definition for myopia using logMAR VA >0.3 as the criteria. 1334 Chinese schoolchildren (mean age 7.8; range 7-9 years) were enrolled in the study after those who had hyperopia > or =+2.00 dioptres (D) and astigmatism > = -2.00 D were excluded. Uncorrected logMAR VA was measured for both eyes. Cycloplegia autorefraction was achieved by the instillation of three drops of 1% cyclopentolate 5 minutes apart. The average of five successful consecutive refraction and keratometry readings were obtained with calibrated Canon RK5 autokeratorefractometers by well trained optometry students, at least 30 minutes after the instillation of the third drop of cyclopentolate. SE cut-off points (-0.25 D, -0.5D, -0.75 D, -1.0 D) were evaluated. Using different SE cut-off points, the myopia prevalence rates of this sample of schoolchildren varied from 45.8% (SE at least -0.25 D) to 30.7% (SE at least -1.0 D). The cut-off point of > or =-0.75 D had a sensitivity and specificity of 91.8% (95% CI, 89.2 to 94.4) and 93.7% (95% CI, 92.1 to 95.3), respectively, to predict low vision defined as uncorrected logMAR VA > 0.3 (either eye). The next best cut-off point of -0.5D had a higher sensitivity (93.3%), but lower specificity (87.9%). The cut-off points of -0.75D and -0.5D in SE refraction are appropriate for the prediction of uncorrected logMAR VA worse than 0.3, which is the criterion for the US common state adult driver licensing standard.
Flow-Chart of patient sets and protocol deviations. 
Primary efficacy variable-clinical cure in the worse eye on D9 
To compare the efficacy and safety of Azyter, azithromycin 1.5% eye drops, for 3 days with tobramycin 0.3% for 7 days to treat purulent bacterial conjunctivitis. This was a multicentre, randomised, investigator-masked study including 1043 children and adults with purulent bacterial conjunctivitis. Patients received either azithromycin 1.5% twice-daily for 3 days or tobramycin 0.3%, 1 drop every two hours for 2 days, then four times daily for 5 days. Clinical signs were evaluated and cultures obtained at D0, D3 and D9 (where D refers to "day"). Primary variable was the clinical cure at the Test-of-Cure (TOC)-visit (D9+/-1), for patients with D0-positive cultures. The cure was defined as: bulbar conjunctival injection and discharge scores of 0. Among 471 patients with D0-positivity in the per protocol set, 87.8% of the azithromycin 1.5% group and 89.4% of the tobramycin group were clinically cured at the TOC-visit. Azithromycin was non-inferior to tobramycin for clinical and bacteriological cure. Clinical cure was significantly higher with azithromycin 1.5% at D3. The safety profile of azithromycin was satisfactory with a good patient and investigator's acceptability. Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children.
The ocular effects of the alpha-adrenoceptor blocking drug bunazosin, administered as eyedrops, have been measured in a placebo-controlled double-blind single-dose study in 15 healthy volunteers. The drug significantly reduced intraocular pressure over 10 hours, and there was no associated change in pulsatile ocular blood flow. Characteristic effects of alpha-adrenoceptor blockade were observed--miosis, ptosis, and conjunctival hyperaemia. The miosis alone persisted for more than 24 hours in nine out of 15 subjects.
In a group of 68 patients a double-blind study was performed to assess the effect of preoperative oxybuprocaine 0.4% (Dorsacaine, Novesin) eye drops in comparison with a placebo in preventing surgically induced miosis during extracapsular cataract extraction. One drop of oxybuprocaine 0.4% or placebo was instilled 10 and 5 minutes preoperatively. The pupil diameter was recorded at different stages of the operation. It was found that oxybuprocaine reduced the amount of pupil constriction during the operation significantly as compared with the placebo group, facilitating the removal of lens material and the implantation of an intraocular lens. The effect of oxybuprocaine is considered to be due to anaesthetic action on sensory nerves in the eye, which may inhibit the release of a miotic substance.
[corrected] The aim of this study was to compare the efficacy and safety of 4% articaine with a mixture containing equal volumes of 2% lidocaine and 0.5% levobupivacaine without hyaluronidase for sub-Tenon's anaesthesia in phacoemulsification cataract surgery. The study was a prospective, randomised double-masked clinical trial of 65 patients allocated to receive either 4% articaine or a mixture containing equal parts of 2% lidocaine and 0.5% levobupivacaine. All patients had pre- and postoperative Hess charting to document ocular motility dysfunction. Ocular and eyelid movements were scored at 2 min intervals from 2 to 10 min after injection of the anaesthetic agent, and at the end of surgery. Complications related to injection, including pain, chemosis and subconjunctival haemorrhage, were recorded. Patients rated pain (none/mild/moderate/severe) during surgery. The operating surgeon masked to the anaesthetic agent assessed proptosis/chemosis at the start of the operation and the degree of ocular akinesia and analgesia at the end of surgery. The articaine group demonstrated a rapid onset of ocular akinesia with a mean time to readiness for surgery (achieving a score of </=5) of 4.0 min compared with 10 min for the lidocaine/levobupivacaine group (p = 0.001). The effectiveness of block was significantly greater in the articaine group at all points (p<0.01). Surgeons rated ocular akinesia to be superior in the articaine group (p<0.001). Patients and surgeons rated the analgesic effect as comparable in either group. Eyelid scores, subconjunctival haemorrhage and chemosis were comparable in either group. Hess chart was performed on all patients pre- and postoperatively. There was no clinically significant motility disturbance in the articaine group, whereas one patient in the lidocaine/levobupivacaine group developed diplopia with abnormal ocular motility on the Hess chart. Articaine (4%) is a safer and a superior anaesthetic agent than a mixture of 2% lidocaine and 0.5% levobupicaine in achieving ocular akinesia for sub-Tenon's block in phacoemulsification cataract surgery.
Right cornea before treatment, showing typical severe crystal deposition. Figure 2 Right cornea after treatmentfor three months, showing virtually complete clearance ofcrystals except in the extreme periphery. 
Right cornea before treatment, showing typical severe crystal deposition. Figure 2 Right cornea after treatmentfor three months, showing virtually complete clearance ofcrystals except in the extreme periphery. 
A 2-year-old girl with nephropathic cystinosis was successfully treated with topical cysteamine 0.5% to one eye. Clearance of crystals from the treated cornea was virtually complete after three months. The possibilities and limitations of this form of treatment are discussed.
A double-masked controlled clinical trial of 5% unpreserved tolmetin versus 0.5% prednisolone versus 0.9% saline in acute endogenous nongranulomatous anterior uveitis was carried out on 100 patients. 69% of the prednisolone-treated patients were judged "cured" at the end of the 3-week study. This is compared with a cure rate of 47% for the tolmetin-treated patients for 53% for the placebo (saline) group. No statistically significant difference was established between the 3 groups.
We read with great interest the recent article ‘Efficacy of systemic propranolol for severe infantile haemangioma of the orbit and eyelid: a case study of eight patients’, advocating oral propranolol as first-line therapy for periocular capillary haemangiomas.1 We would like to add topical timolol to the available treatment options, which was not mentioned in the article. It has been the experience of several published cohorts, as well as our own …
Horner syndrome in left eye. (A) Baseline condition, miosis and ptosis in left eye. (B) No change in the left eye 1 hour following 10% cocaine instillation. (C) Anisocoria reversal and lid elevation in the left eye 1 hour after instillation of 0.5% apraclonidine. 
Pupil size and upper lid level changes (SD) (mm) of the groups
Bilateral OSP caused by diabetes mellitus. (A) Baseline condition, bilateral miosis and ptosis. (B) No change 1 hour later 10% cocaine instillation. (C) Bilateral dilation and lid elevation 1 hour after instillation of 0.5% apraclonidine. 
Pseudo-Horner syndrome. (A) Baseline anisocoria. (B) Symmetrical dilation of both pupils 1 hour after 10% cocaine instillation. (C) Symmetrical bilateral miosis 1 hour after instillation of 0.5% apraclonidine. 
To evaluate the sensitivity and specificity of 0.5% apraclonidine test in the diagnosis of oculosympathetic paresis (OSP). Apraclonidine (0.5%) was administered to 31 eyes, nine with a diagnosis of Horner syndrome (HS), 22 with bilateral OSP caused by diabetes, and to 54 control eyes. All were confirmed with the cocaine test. The effects on pupil diameter and upper eyelid level were observed 1 hour later. Apraclonidine caused a mean dilation of 2.04 mm (range 1--4.5) (p<0.001) in the pupils with OSP and it caused pupillary constriction in the control eyes with a mean change of -0.14 mm (range 0.5 to --1) (p<0.05). It caused reversal of anisocoria in all HS cases. Its effects on both pupil diameters and upper lid levels differed significantly between the groups (p<0.001). The mean elevation in the upper lid was 1.75 mm (range 1--4) in the OSP group (p<0.001) and 0.61 mm (range 0--3) in the control group (p<0.001). The effect of the apraclonidine (0.5%) test on the pupil diameter was diagnostic for OSP and had at least the same sensitivity and specificity as the cocaine test for the diagnosis of OSP.
A trial of a mixture of guanethidine 5% and adrenaline 0.5% (Ganda 5.05) and of guanethidine 3% and adrenaline 0.5% (Ganda 3.05) was conducted on 90 eyes in 53 patients with open-angle glaucoma or ocular hypertension. The cases fell into 5 groups: untreated cases, cases on pilocarpine 1%, on pilocarpine 2%, on pilocarpine 2 to 4% and adrenaline 1%, and on separate guanethidine 5% and adrenaline 1%. Baseline pressures and average pressures on the previous treatment were established. Substitution with Ganda 3.05 or 5.05 was started, and the patients attended 2 weeks, 1 month, 3 months, and 6 months from the start of the trial. Applanation tonometry was carried out at the same time of day. The pupil was measured, ptosis and superficial punctate corneal staining were looked for and evaluated, and the patients were questioned for symptoms of side effects and acceptability. All the eyes that had previously been treated with pilocarpine 1% or 2% presented significantly lower intraocular pressures on Ganda 3.05. The patients on pilocarpine 4% and adrenaline 1% also had lower intraocular pressures on Ganda 5.05, but the significance was less, and the patients on separate guanethidine and adrenaline had a small but not statistically significant drop in pressure. Ptosis and discomfort were evaluated on a subjective scale. Patient acceptability was good. The trial was interrupted in 5 cases for various reasons. Tachyphylaxis and tolerance to the mixtures were not observed in this series.
Top-cited authors
Silvio Paolo Mariotti
  • World Health Organization WHO
Paul Mitchell
  • Westmead Institute for Medical Research
T-Y Wong
  • Singapore National Eye Centre
Joel S Schuman
  • NYU Tandon School of Engineering
Harminder Dua
  • University of Nottingham