Thomas R Friberg’s research while affiliated with University of Pittsburgh and other places

Purpose Description of longitudinal follow-up of 13 patients diagnosed with Idiopathic Multifocal Pigment Epithelial Detachments (IMPED), a rare condition first described by Gass et al., in 2005. Methods This retrospective case series included 13 patients in the first to sixth decades of life who presented with multiple bilateral PEDs, confirmed by Optical Coherence Tomography. Ancillary imaging included fundus autofluorescence and angiography to exclude alternative diagnoses such as Central Serous Chorioretinopathy and Polypoidal Choroidovasculopathy. Electrophysiology testing, including full-field electroretinography (FFERG) and electrooculography (EOG), assessed both retinal and pigment epithelium function. Visual acuity (VA) was documented over a mean follow-up of 6.5 years (range: 0.1–26.4 years). Results All patients demonstrated stable VA during follow-up. Electrophysiology was normal in tested patients (FFERG: 9/13, EOG: 7/13). Genetic testing (10/13) was non-diagnostic. Two patients (including a patient previously receiving anti-VEGF without exudation) exhibited outer retinal atrophy. One patient developed a choroidal neovascularization (CNV) during follow-up, which resolved with intravitreal aflibercept. Conclusion IMPED should remain a diagnosis of exclusion, confirmed after sufficient follow-up demonstrating no progression. While our study implies a generally favorable prognosis, continuous monitoring is necessary to assess long-term risks, including potential complications such as the development of CNV and/or atrophy.

Background: With the clinical advances in the field of gene therapy, the development of objective measures of visual function of patients with inherited retinal dystrophies (IRDs) is of utmost importance. Here, we propose one such measure. Methods: We retrospectively analyzed data from a cohort of 194 eyes of 97 genetically diagnosed patients with retinitis pigmentosa (RP), the most common IRD, followed at the UPMC Vision Institute. The analyzed data included the reflectivity ratio (RR) of the retinal nerve fiber layer (RNFL) to that of the entire retina, visual acuity (VA) and the thickness of the retinal outer nuclear layer (ONL) and the RNFL. Results: There was a strong positive correlation between the RR and VA. Both VA and the RR were negatively correlated with disease duration; VA, but not the RR, was negatively correlated with age. The RR correlated with the ONL but not with the RNFL thickness or the intraocular pressure. Age, RR, disease duration and ONL thickness were found to be independent predictors of VA by multivariate analysis. Conclusion: The OCT RR could serve as an independent predictor of visual acuity, and by extension of retinal function, in genetically diagnosed RP patients. Such objective measures can be of great value in patient selection for therapeutic trials.

Purpose Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as “masqueraders of uveitis”. Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. Methods An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. Results We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). Conclusion This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Objective: To identify characteristics and visual outcomes of coagulase-negative staphylococci (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study. Design: Single-centre retrospective analysis. Participants: Forty-two samples from 40 patients with documented CoNS endophthalmitis. Methods: Visual acuity outcomes of patients with CoNS endophthalmitis were assessed in relation to species and type of treatment instituted (e.g., pars plana vitrectomy [PPV] versus tap and injection of intravitreal antibiotics [T&I]). Strains were speciated using Gram and Giemsa staining and were further identified using API Staph and Biolog GEN III microplates. Genetic analysis was performed via polymerase chain reaction. Antibiotic susceptibility was assessed with disk diffusion. Results: Staphylococcus epidermidis was the most prevalent CoNS in our study. Cataract surgery and intravitreal injections were the most common sources for acute CoNS endophthalmitis. Eyes presenting with hand motion or better vision had similar mean final vision after either intravitreal antibiotics or PPV, whereas those with light perception or worse vision at onset had better outcomes after PPV only. Subanalysis showed that patients with S. epidermidis endophthalmitis (n = 39 eyes) had similar visual outcomes with either intravitreal injections or PPV regardless of visual acuity. Hypopyon and vitritis are not always present. Conclusions: Patients with S. epidermidis endophthalmitis may benefit similarly from either early vitrectomy or intravitreal antibiotic injections regardless of visual acuity. This finding complements the management standards set forth by the Endophthalmitis Vitrectomy Study.

Importance Low dietary nitrate intake has previously been suggested to be a risk factor for age-related macular degeneration (AMD) progression; however, this finding has not been replicated in other cohorts or adjusted for dietary patterns. Objective To determine whether there is an association between dietary nitrate intake and AMD progression. Design, Setting, and Participants This cohort study analyzed data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and their extended follow-up studies, which were conducted in multicenter outpatient retinal practices. Participants in both trials had non–late AMD in at least 1 eye. Data were analyzed from March 1, 2020, to September 30, 2022. Exposure Dietary nitrate intake. Main Outcomes and Measures Association between dietary nitrate intake and development of late AMD (neovascular AMD [nAMD] or geographic atrophy [GA]) or large drusen. The interactions of dietary patterns, with common at-risk single-nucleotide polymorphisms, were also assessed. Results In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants [110 of whom participated in both studies]), there were 13 511 eligible eyes. The combined cohort comprised 4396 women (56%) and 3392 men (44%), and the combined mean (SD) age was 71.1 (6.6) years. Dietary nitrate intake was associated with a decreased risk of progression to late AMD in the combined AREDS/AREDS2 cohort (hazard ratio [HR], 0.77 [95% CI, 0.69-0.86] for quartile 4 vs quartile 1 of intake) and a decreased risk of GA (HR, 0.71 [95% CI, 0.61-0.83]) and nAMD (HR, 0.85 [95% CI, 0.73-0.99]). In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD (HR, 0.77 [95% CI, 0.65-0.91]) and GA (HR, 0.80 [95% CI, 0.65-0.97]) but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD (HR, 0.90 [95% CI, 0.80-1.02]) or nAMD (HR, 0.93 [95% CI, 0.78-1.11]). There was a correlation between Mediterranean dietary patterns and dietary nitrate intake ( r = 0.52, P < .001). Conclusions and Relevance The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. These results are subject to potential bias and are hypothesis-generating in nature; therefore, they are insufficient to support new clinical recommendations. Previously described associations between dietary nitrate intake and AMD may in fact represent overall dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.

Importance: After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. Objective: To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). Design, setting, and participants: This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. Interventions: During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Main outcomes and measures: Self-reported lung cancer and late AMD validated with medical records. Results: This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Conclusions and relevance: Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

Background and objective: Retina specialists use lidocaine gel as a topical anesthetic. We determined the antibacterial interaction between povidone-iodine (PI) and lidocaine gel using corneoscleral tissue as a solid phase medium. Materials and methods: Five pieces of corneoscleral tissue in five trials were inoculated with 1.000 colony-forming units of bacteria isolated from endophthalmitis. Inoculated corneal tissue were overlaid with nothing (control), lidocaine gel, 5% PI, lidocaine gel over 5% PI, and 5% PI over lidocaine gel for 5 minutes prior to placement in growth liquid medium at 37°C. Growth was monitored for 48 hours. Results: Application of lidocaine gel prior to 5% PI application provided for the growth of the five bacterial isolates, whereas 5% PI prior to lidocaine gel prevented growth. Conclusion: Using corneoscleral tissue, PI and lidocaine gel appear to have an antagonistic interaction when lidocaine gel is applied initially prior to 5% PI, preventing bactericidal activity of PI. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:S13-S16.].

Scleral buckling is a method of reattaching the neurosensory retina to the retinal pigment epithelium when retinal detachment occurs. While the buckle procedure has high success rates in terms of reattaching the retina, the forces created by encircling and segmental buckles can alter the biomechanical properties of the eye and many of its structures, including axial length, corneal power, astigmatism, corneal hysteresis, corneal resistance factor, anterior chamber depth, ocular volume, ocular rigidity, and ocular blood flow. This chapter delves into the biomechanical changes induced by scleral buckling.