Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma.

Pigmentary glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called pigment dispersion syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used whole exome sequencing of two independent pedigrees to identify two premelanosome protein (PMEL) variants associated with heritable PDS/PG. PMEL encodes a key component of the melanosome, the organelle essential for melanin synthesis, storage and transport. Targeted screening of PMEL in three independent cohorts (n = 394) identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein. In addition, analysis of PDS/PG-associated PMEL variants expressed in HeLa cells revealed structural changes to pseudomelanosomes indicating altered amyloid fibril formation in five of the nine variants. Introduction of 11-base pair deletions to the homologous pmela in zebrafish by the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 method caused profound pigmentation defects and enlarged anterior segments in the eye, further supporting PMEL's role in ocular pigmentation and function. Taken together, these data support a model in which missense PMEL variants represent dominant negative mutations that impair the ability of PMEL to form functional amyloid fibrils. While PMEL mutations have previously been shown to cause pigmentation and ocular defects in animals, this research is the first report of mutations in PMEL causing human disease.

The influence of etiology on surgical outcomes in neovascular glaucoma.

BACKGROUND: The authors sought to evaluate visual outcomes in patients with varying etiologies of neovascular glaucoma (NVG), who were treated with glaucoma drainage devices (GDD). METHODS: This was a retrospective case series of patients at a large academic teaching institution who had surgical intervention for neovascular glaucoma between September 2011 and May 2019. Eyes were included if there was documented neovascularization of the iris/angle with an intraocular pressure (IOP) > 21 mmHg at presentation. Eyes must also have been treated with surgical intervention that included a GDD. Primary outcome measure was visual acuity at the 1-year post-operative visit. Secondary outcome measure was qualified success after surgery defined by: pressure criteria (5 mmHg < IOP ≤ 21 mmHg), no re-operation for elevated IOP, and no loss of LP vision. RESULTS: One hundred twenty eyes met inclusion criteria. 61.7% had an etiology of proliferative diabetic retinopathy (PDR), 23.3% had retinal vein occlusions (RVO), and the remaining 15.0% suffered from other etiologies. Of patients treated with GDD, eyes with PDR had better vision compared to eyes with RVO at final evaluation (p = 0.041). There was a statistically significant difference (p = 0.027) in the mean number of glaucoma medications with Ahmed eyes (n = 70) requiring 1.9 medications and Baerveldt eyes (n = 46) requiring 1.3 medications at final evaluation. CONCLUSIONS: In our study, many patients with NVG achieved meaningful vision, as defined by World Health Organization (WHO) guidelines, and IOP control after GDD. Outcomes differed between patients with PDR and RVO in favor of the PDR group. Different GDD devices had similar performance profiles for VA and IOP outcomes. Direct prospective comparison of Baerveldt, Ahmed, and cyclophotocoagulation represents the next phase of discovery.

Evidence-based management of primary angle closure glaucoma.

PURPOSE OF REVIEW: To review the classification of primary angle closure (PAC) and discuss the evidence-based management of each type. RECENT FINDINGS: There is limited evidence to support the prophylactic treatment of primary angle closure suspects. Cataract and clear lens extraction may be more effective than traditional therapy in controlling intraocular pressure (IOP) in patients with PAC, primary angle closure glaucoma, and acute angle closure crisis. SUMMARY: Treatment of angle closure depends on the signs of chronic angle damage and glaucomatous optic neuropathy. In the absence of such evidence, serial gonioscopy may be the preferred therapy. If signs or symptoms are present, medical therapy and laser peripheral iridotomy are beneficial. However, recent data suggest that cataract extraction may be more effective at controlling the IOP than laser or incisional glaucoma procedures.

Glaucoma Tube Outcomes with and without Anti-VEGF in Patients with Age-related Macular Degeneration.

PURPOSE: To compare glaucoma tube outcomes of wet age-related macular degeneration (AMD) eyes receiving anti-VEGF injections versus dry AMD eyes and no anti-VEGF. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: Patients with wet AMD and a history of anti-VEGF within a year prior or after stand-alone glaucoma tube surgery and eyes with dry AMD and no history of anti-VEGF with at least 6 months of follow-up. Eyes with neovascular glaucoma or anti-VEGF for reason other than wet AMD were excluded. METHODS: A Kaplan-Meier analysis compared survival for wet versus dry AMD eyes. Failure was defined as intraocular pressure (IOP) > 21 mmHg or < 20% IOP reduction from baseline or IOP ≤ 5 mmHg for 2 consecutive postoperative visits starting at month 3, additional glaucoma surgery, or no light perception. Complete success was defined as no failure or medications at final follow-up. Hypertensive phase was defined for valved tubes as IOP > 21 mmHg within 3 months of surgery after a reduction to < 22 mmHg during the first postoperative week. Intraocular pressure, percent reduction in IOP, number of glaucoma medications, and early (< 1 year) and late (> 1 year) complications were compared through 5 years. MAIN OUTCOME MEASURES: Survival analysis, IOP, number of medications. RESULTS: Baseline IOP, number of medications, or tube type were not significantly different between wet (n = 24) and dry AMD eyes (n = 54). No wet AMD eyes failed versus 10 (18%) dry AMD eyes (P = 0.03). Five-year survival was estimated as 100% for wet AMD and 72% for dry AMD (P = 0.04). Wet AMD eyes had lower IOP (10.6 vs. 12.7 mmHg, P = 0.05), greater IOP reduction (60% vs. 49%, P = 0.04), fewer medications (1.2 vs. 2.1, P = 0.02), and more complete success (50% vs. 15%, P = 0.001) at final follow-up (32 vs. 36 months, P = 0.42). Fewer wet than dry AMD eyes experienced hypertensive phase (0/10 [0%] vs. 4/10 [40%], P = 0.04). There were no significant differences in early or late complications. CONCLUSIONS: Exposure to anti-VEGF may influence postoperative wound healing and capsule formation which may improve glaucoma tube surgical outcomes. Prospective data is needed to consider perioperative administration of anti-VEGF for glaucoma tube surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk Factors for Flat Anterior Chamber Requiring Intervention After Glaucoma Drainage Implant: A Retrospective Case-Controlled Study.

PURPOSE: To identify risk factors for flat anterior chamber that required additional intervention in the postoperative period (90 days) after uncomplicated Baerveldt Glaucoma Implant (BGI) surgery. DESIGN: Retrospective, matched case-control study. METHODS: A total of 42 cases (eyes) that received BGI at Anne Bates Leach Eye Hospital between February 1, 2011, and January 1, 2019, and that developed flat anterior chamber were included. For each case, we matched 2 controls (84). Variables included sex, diagnosis, diabetes, hypertension, pre- and postoperative glaucoma medications, ocular conditions, and intraocular pressure (IOP). Multivariable conditional logistic regression determined odds ratios (ORs) for independent predictors. RESULTS: Case patients were more likely to be female (69.1% case patients/41.7% controls), to have a history of taking oral carbonic anhydrase inhibitors (CAIs) at tube opening (21.4%/7.1%), to be of another race/ethnicity (11.9%/0.0%), and to have pseudoexfoliation (23.8%/6.0%), and were less likely to be using cholinergic agonists (0.0%/11.9%) at baseline and to have primary open angle glaucoma (42.9%/64.3%). Case patients had greater mean age (75.9/64.9 years), earlier tube opening time (5.6/6.2 weeks), and lower IOP after tube opening (7.2/14.4 mm Hg), but IOP before opening was higher (24.7/19.5 mm Hg). We identified 3 independent predictors: older age (10-year increase OR = 3.59, P < .0001), oral CAI use at tube opening (OR = 5.65, P = .009), and higher IOP prior to tube opening (3 mm Hg increase OR = 1.30, P = .018). CONCLUSION: Risk factors for flat anterior chamber were older age, oral CAIs at tube opening, and higher IOP before tube opening. Strategies to minimize the acute IOP reduction that preceded this complication such as discontinuing oral CAI prior to tube opening may be considered.

The Effect of Changing Fellowship Interview Format on Candidate Ranking Variabilities: The COVID-19 Experience.

Purpose: This study investigated the effect of interview format changes (in-person to virtual, one-to-one to multiple-to-one) necessitated by the COVID-19 travel restrictions on preliminary fellowship candidate ranking variabilities. Design: Cross-sectional observational study. Method: In 2018 and 2019, the glaucoma fellowship interviews were conducted in-person in a one-to-one format, whereas in 2020, interviews were virtual and in a multiple (interviewers)-to-one (candidate) format. We compared ranking ranges of interviewers within the same virtual room (WSR) and not within the same virtual room (NWSR) to assess the effect of WSR versus NWSR on ranking variabilities. We also compared ranking categories ("accept," "alternate," and "pass") agreements between 2018, 2019, and 2020 to assess the effect of virtual versus in-person interviews on ranking variabilities. Results: NWSR and WSR mean rankings differed by 1.33 (95% confidence interval difference 0.61 to 2.04, p = 0.0003), with WSR interviewers having less variability than NWSR pairs. The variability between 2018/2019 (in-person interviews) and 2020 (virtual interviews) showed no differences between in-person and virtual interviews (weighted Kappa statistic 0.086 for 2018, 0.158 for 2019, and 0.101 for 2020; p < 0.05 for all years). The overall least attractive candidate has the lowest variability; the most attractive candidate has the second lowest variability. Conclusion: Grouping interviewers WSR during the interview decreased ranking variabilities compared to NWSR, while a change from in-person to virtual interview format did not increase the ranking variabilities. This suggests that the decreased nonverbal interactions in virtual interviews do not decrease interviewers' perceptions as applied to preliminary rankings.

Glaucoma Cascade Screening in a High Risk Afro-Caribbean Haitian Population: A Pilot Study.

PRCIS: Glaucoma cascade screening in first-degree relatives (FDRs) of young Haitian glaucoma patients had high yield for diagnosing manifest and suspected glaucoma in 30.8% of those screened despite modest participation. PURPOSE: To evaluate the outcomes of glaucoma cascade screening in FDRs (parents, siblings, and offspring) of Haitian juvenile open-angle glaucoma (JOAG) patients. PATIENTS AND METHODS: Consecutive index patients (Haitians with JOAG) were identified, and the number/type of FDRs residing in South Florida were recorded. These FDRs were invited for free glaucoma screening, which included a comprehensive ophthalmic exam, gonioscopy, automated visual field testing and optical coherence tomographic analysis of the retinal nerve fiber layers. FDR characteristics and clinical findings from screening are reported. RESULTS: A total of 77 FDRs were invited, 26 (33.8%) agreed to undergo screening (18 females, 9 males), which revealed 2 (7.7%) with manifest glaucoma (mean age 77.5 y; one of whom was previously unaware of his glaucoma diagnosis), 6 (23.1%) with suspected glaucoma (mean age 29.8±18.3 y), and 18 (69.2%) without manifest or suspected glaucoma (mean age 37.2±21.8 y). Siblings of index patients were least likely to participate in cascade glaucoma screening when compared with index patients' parents or offspring. FDR eyes with manifest glaucoma had significantly worse best-corrected visual acuities, higher intraocular pressures, thinner central corneal thicknesses, and thinner circumferential papillary retinal nerve fiber layer thicknesses than those without glaucoma. CONCLUSION: Glaucoma cascade screening of Haitian JOAG patients' FDRs revealed that 30.8% had suspected or manifest glaucoma. Future efforts centered on provider-initiated recruitment and improving public glaucoma awareness and education may increase screening participation.

Update on aqueous shunts.

Medicare claims data and surveys of the American Glaucoma Society membership show that aqueous shunts are being increasingly utilized in the surgical management of glaucoma. New clinical trials data have identified differences in the efficacy and safety of shunts in common use. Recent studies have reported comparable results with trabeculectomy and aqueous shunts in similar patient groups. Intraoperative and postoperative complications may develop with aqueous shunt surgery related to the implantation of a foreign material. Several modifications in surgical technique have been directed toward improving surgical success, reducing complications, and optimizing efficiency and cost.

Practice preferences for glaucoma surgery: a survey of the american glaucoma society in 2008.

BACKGROUND AND OBJECTIVE: To evaluate glaucoma surgical practice patterns among members of the American Glaucoma Society (AGS). PATIENTS AND METHODS: An anonymous web-based survey was sent to AGS members to determine their preferred surgical approach in ten clinical settings. Survey results were compared with those from 1996 and 2002. RESULTS: A total of 125 (22%) AGS members responded to the survey. Mean glaucoma drainage device (GDD) usage increased from 17.5% (range: 5% to 37%; standard deviation [SD]: 10.9%) in 1996 to 50.8% (range: 15% to 76%; SD: 17.3%) in 2008, and mean trabeculectomy usage decreased from 80.8% (range: 62% to 93%; SD: 11.3%) in 1996 to 45.5% (range: 16% to 80%; SD: 17.9) in 2008. GDD was most popular in none of 8 clinical settings in 1996, and 5 of 8 clinical settings in 2008. Mitomycin C was selected as an adjunctive antifibrotic agent to trabeculectomy in 85% to 99% of cases. CONCLUSION: Glaucoma surgical practice patterns have changed since 1996. The use of a GDD has progressively increased, and the popularity of trabeculectomy decreased between 1996 and 2008. Mitomycin C remains the most frequently selected antifibrotic agent used as an adjunct to trabeculectomy.From Boston Medical Center (MAD), Boston University School of Medicine, Boston, Massachusetts; Bascom Palmer Eye Institute (SJG, WJF, WS, RKP), University of Miami, Miller School of Medicine, Miami, Florida; and the Department of Ophthalmology (PPC), University of Washington, Seattle, Washington.The authors have no financial or proprietary interest in the materials presented herein.Address correspondence to Steven J. Gedde, MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136. E-mail: sgedde@med.miami.edu Received: January 19, 2011 Accepted: March 09, 2011.

Factors Associated With Laser Trabeculoplasty Response Duration: Analysis of a Large Clinical Database (IRIS Registry).

PRCIS: In eyes with trabeculoplasty response, those with lower baseline pressure, angle recession or uveitis had shorter survival. Eyes without medications before treatment remained medication-free for a median of 197 days. PURPOSE: We examined patients in a large clinical registry to assess factors associated with laser trabeculoplasty (LTP) response durations. METHODS: This is a retrospective cohort study with LTP patients in the Intelligent Research in Sight Registry. Data were extracted if the eye had a LTP procedure code and a glaucoma diagnosis. In responders [≥20% intraocular pressure (IOP) reduction], any post-LTP IOP that was above 80% of baseline was considered a failure event. Eyes were censored if IOP-lowering medication/procedure was added/performed, or if the eye reached the end of follow-up. First eye of bilaterally treated patients were included. RESULTS: A total of 79,332 patients/eyes were included; 53.2% female; mean age 71.5 years; 64.5%White; 71.2% primary open angle glaucoma. Mean baseline IOP was 21.6±5.3 mm Hg (2.1±1.5 medications). Eyes with higher baseline IOP had longer survival (>24 mm Hg median 349 d; 18 to 24 mm Hg median 309 d; <18 mm Hg median 256 d, P<0.001 for all comparisons). Overall failure at 0, 6, 12, 18 and 24 months were 0.2%, 6.1%, 16.8%, 29.1%, and 40.8%. Angle recession and uveitis increased the risk of failure (hazard ratios 1.69 and 1.80, respectively). Eyes without medications at baseline remained medication-free for a median of 197 days (interquartile range 106, 395 d). CONCLUSIONS: Angle recession and uveitis increase the risk of LTP failure. LPT may be effective in prolonging medication-free IOP-control in some patients.

Factors Associated With Favorable Laser Trabeculoplasty Response: IRIS Registry Analysis.

PURPOSE: We examined patients in a large clinical registry to assess factors associated with laser trabeculoplasty (LTP) responses. DESIGN: Retrospective cohort study. METHODS: StudyPopulation: LTP patients in the Intelligent Research in Sight (IRIS) Registry, 2013-2018. OBSERVATION: IRIS Registry data were extracted if the eye had a procedural code for LTP and a glaucoma diagnosis. Eyes were excluded if LTP laterality or baseline intraocular pressure (IOP) could not be determined. Following LTP, "nonresponders" were those with <20% IOP reduction after 8 weeks, while "responders" were those with ≥20% IOP reduction. MainOutcomeMeasures: Proportion of responders, odds ratios (OR) of pre-LTP factors associated with being a nonresponder. RESULTS: A total of 263,480 eyes were included, with mean age 71.4 ± 11.7 years. Mean baseline IOP was 19.1 ± 5.0 mm Hg, mean number of pre-LTP medications was 2.1 ± 1.5. Response rate was 36.9% overall and 68.8% for those with baseline IOP >24 mm Hg. Higher baseline IOP was associated with reduced odds of nonresponse (OR = 0.60, P < .0001 for a 3 mm Hg increase). Angle recession, uveitis, and aphakia increased the odds of a nonresponse (ORs 2.46, 1.50 (both P < .0001), and 1.55 (P = .0259), respectively). In nonresponders with at least 1 medication at baseline, 76.3% of eyes had fewer medications postoperatively. CONCLUSIONS: Lower baseline IOP, angle recession, uveitis, and aphakia were associated with increased odds of nonresponse. Future studies that analyze LTP responder survival and implementation lag would facilitate resource optimization in glaucoma therapy.

The Tube Versus Trabeculectomy IRIS® Registry Study: Cohort Selection and Follow-up and Comparisons to the Randomized Controlled Trial.

PURPOSE: To assess the feasibility of replicating a randomized controlled trial (RCT) with a cohort of eyes, from IRIS® Registry data, analogous to the Tube Versus Trabeculectomy (TVT) RCT cohort and compare characteristics and follow-up. DESIGN: Comparison of RCT and IRIS Registry cohorts and follow-up. METHODS: We identified a cohort of IRIS Registry eyes (2013-2017) that received either a glaucoma drainage implant (tube) or trabeculectomy after a previous trabeculectomy and/or cataract extraction; extracted clinical and demographic characteristics for baseline surgery and follow-up visits through 1 year; and compared treatment groups in the IRIS Registry cohort and this cohort to the TVT RCT cohort. RESULTS: The IRIS Registry cohort included 419 eyes: 183 (43.7%) trabeculectomy; 236 (56.3%) tube. There were significant differences between treatment groups, including race (White: trabeculectomy 61.8%, tube 44.9%; Black: trabeculectomy 20.8%, tube 35.6%; P = .003) and the percentage of follow-up visits completed (trabeculectomy 88.4%, tube 83.8%, P = .004). There were also significant differences between the TVT IRIS Registry cohort and the TVT RCT cohort in the percentage of follow-up visits completed (IRIS Registry 85.6%, RCT 96.1%, P < .001) and in the probability of having a 1-year follow-up visit (IRIS Registry 81.4%, RCT 89.2%, P = .011). CONCLUSION: The TVT IRIS Registry cohort had several significant treatment group differences at baseline, whereas there had been none in the TVT RCT cohort. Follow-up in the TVT IRIS Registry cohort was inferior to that of the TVT RCT. Some data needed to refine the selection of eyes for the cohort were not available in the IRIS Registry.

Tube Versus Trabeculectomy IRISⓇ Registry 1-Year Composite Outcome Analysis with Comparisons to the Randomized Controlled Trial.

PURPOSE: This study compared 1-year results for the composite treatment outcome from the Tube Versus Trabeculectomy (TVT) randomized controlled trial (RCT) to those from an IRISⓇ (Intelligent Research In Sight) Registry cohort of analogous eyes. DESIGN: Retrospective clinical study with comparison to an RCT. METHODS: Subjects' eyes in the IRIS Registry received either a glaucoma drainage implant (tube) or underwent trabeculectomy after a previous trabeculectomy and/or cataract extraction and had data for 1-year follow-up analyses. OUTCOME: Eyes were classified as failing if they had hypotony (intraocular pressure (IOP) ≤5 mm Hg) or inadequate IOP control (IOP >21 mm Hg or not reduced at least 20% below baseline) on 2 consecutive follow-up visits after 3 months, a reoperation for glaucoma, or no light perception vision and as successful otherwise. Failure risk was compared by treatment, demographic, and clinical variables and was compared to analogous failure risks from the TVT RCT. RESULTS: The TVT IRIS Registry cohort included 419 eyes, 236 tube eyes (56.3%) and 183 trabeculectomy eyes (43.7%). In this cohort, there was no significant failure risk difference (12.3% for tube eyes and 16.4% for trabeculectomy eyes, P = 0.231). Comparing the studies, there was a significantly greater risk of failure in the TVT IRIS Registry tube eyes than in the TVT RCT tube eyes (3.8%; P <.001). Reasons for treatment failure included reoperations for glaucoma (none in the TVT RCT at 1 year). CONCLUSIONS: Our results were different from those in the TVT RCT. Possible reasons include non-Baerveldt tubes, greater severity among tube eyes, and practice patterns that reflect real-world data, which are different than those in RCTs.

Assessment of Cumulative Incidence and Severity of Primary Open-Angle Glaucoma Among Participants in the Ocular Hypertension Treatment Study After 20 Years of Follow-up.

Importance: Ocular hypertension is an important risk factor for the development of primary open-angle glaucoma (POAG). Data from long-term follow-up can be used to inform the management of patients with ocular hypertension. Objective: To determine the cumulative incidence and severity of POAG after 20 years of follow-up among participants in the Ocular Hypertension Treatment Study. Design, Setting, and Participants: Participants in the Ocular Hypertension Treatment Study were followed up from February 1994 to December 2008 in 22 clinics. Data were collected after 20 years of follow-up (from January 2016 to April 2019) or within 2 years of death. Analyses were performed from July 2019 to December 2020. Interventions: From February 28, 1994, to June 2, 2002 (phase 1), participants were randomized to receive either topical ocular hypotensive medication (medication group) or close observation (observation group). From June 3, 2002, to December 30, 2008 (phase 2), both randomization groups received medication. Beginning in 2009, treatment was no longer determined by study protocol. From January 7, 2016, to April 15, 2019 (phase 3), participants received ophthalmic examinations and visual function assessments. Main Outcomes and Measures: Twenty-year cumulative incidence and severity of POAG in 1 or both eyes after adjustment for exposure time. Results: A total of 1636 individuals (mean [SD] age, 55.4 [9.6] years; 931 women [56.9%]; 1138 White participants [69.6%]; 407 Black/African American participants [24.9%]) were randomized in phase 1 of the clinical trial. Of those, 483 participants (29.5%) developed POAG in 1 or both eyes (unadjusted incidence). After adjusting for exposure time, the 20-year cumulative incidence of POAG in 1 or both eyes was 45.6% (95% CI, 42.3%-48.8%) among all participants, 49.3% (95% CI, 44.5%-53.8%) among participants in the observation group, and 41.9% (95% CI, 37.2%-46.3%) among participants in the medication group. The 20-year cumulative incidence of POAG was 55.2% (95% CI, 47.9%-61.5%) among Black/African American participants and 42.7% (95% CI, 38.9%-46.3%) among participants of other races. The 20-year cumulative incidence for visual field loss was 25.2% (95% CI, 22.5%-27.8%). Using a 5-factor baseline model, the cumulative incidence of POAG among participants in the low-, medium-, and high-risk tertiles was 31.7% (95% CI, 26.4%-36.6%), 47.6% (95% CI, 41.6%-53.0%), and 59.8% (95% CI, 53.1%-65.5%), respectively. Conclusions and Relevance: In this study, only one-fourth of participants in the Ocular Hypertension Treatment Study developed visual field loss in either eye over long-term follow-up. This information, together with a prediction model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT00000125.

Virtual Versus In-Person Surgical Fellowship Interviews and Ranking Variability: the COVID-19 Experience.

Objective: To investigate the effect of interview format changes (in-person to virtual, one-to-one to multiple-to-one) necessitated by the COVID-19 travel restrictions on candidate ranking variabilities. Method: In 2018/2019, the glaucoma fellowship interviews were conducted in-person and one-to-one, whereas in 2020, interviews were virtual and multiple (interviewers)-to-one (candidate). We compared ranking ranges of interviewers within the same virtual room (WSR) and not within the same virtual room (NWSR) to assess the effect of this change on ranking variabilities. We also compared ranking categories ("accept," "alternate," and "pass") agreements between in-person and virtual interviews to assess the effect of this change on ranking variabilities. Results: NWSR and WSR mean rankings differed by 1.33 (95% confidence interval difference 0.61 to 2.04, p = 0.0003), with WSR interviewers having less variability than NWSR pairs. The variability of in-person interviews and later virtual interviews showed no differences (weighted Kappa statistic 0.086 for 2018, 0.158 for 2019, and 0.101 for 2020; p < 0.05 for all years). The overall least attractive candidate has the lowest variability; the most attractive candidate has the second lowest variability. Conclusion: Grouping interviewers decreased ranking variabilities, while a change from in-person to virtual interview format did not increase the ranking variabilities.

Review of results from the Tube Versus Trabeculectomy Study.

PURPOSE OF REVIEW: The Tube Versus Trabeculectomy (TVT) Study is a multicenter randomized clinical trial comparing the safety and efficacy of tube-shunt surgery to trabeculectomy with mitomycin (MMC) in eyes with previous cataract and/or unsuccessful glaucoma surgery. This article reviews published results from the TVT Study. RECENT FINDINGS: Tube-shunt surgery had a higher success rate than trabeculectomy with MMC during the first 3 years of follow-up. Trabeculectomy with MMC produced greater intraocular pressure (IOP) reduction in the early postoperative period compared with tube-shunt placement, but similar IOPs were observed after 3 months. Tube-shunt surgery was associated with greater use of adjunctive-medical therapy than trabeculectomy with MMC during the first 2 years of the study, but no difference in medication use was seen at 3 years. The incidence of postoperative complications was higher after trabeculectomy with MMC compared with tube-shunt surgery, but serious complications associated with vision loss and/or reoperation developed with similar frequency after both surgical procedures. No difference in the rate of vision loss was present following trabeculectomy with MMC and tube-shunt surgery after 3 years of follow-up. Cataract progression was common, but occurred with similar frequency with both procedures. SUMMARY: Intermediate-term results of the TVT Study support the expanded use of tube shunts beyond refractory glaucomas. Tube-shunt surgery is an appropriate surgical option in patients who have undergone prior cataract and/or unsuccessful filtering surgery.

Structural-functional dissociation in presumed ethambutol optic neuropathy.

A 55-year-old man with pulmonary Mycobacterium avium intracellulare infection developed decreased vision to 3/200 in the right eye, and 20/200 in the left eye, 11 months after starting ethambutol, rifampin, and isoniazid. A diagnosis of presumed ethambutol optic neuropathy was made, and the medications were discontinued. Visual acuity gradually improved to 20/30 and 20/70 over a period of 34 months. Despite improved central vision and visual field, the patient developed progressive bilateral optic disc cupping, disc pallor, and diffuse nerve fiber layer loss on optical coherence tomography. The observed optic nerve head structural changes in this patient did not correlate with the markedly improved visual function. Visual improvement may occur in ethambutol optic neuropathy despite progressive structural changes.

The Value and Caveats of Interpreting Small Case Series: Implications for Patient Care.

PURPOSE: To discuss the value and limitations of interpreting small case series for the purpose of understanding the pathophysiology of conditions affecting the visual system and how they may influence patient care decision making. DESIGN: Selective review of English-language ophthalmic articles published in peer-reviewed journals since 1950. METHODS: Author-initiated PubMed Central query of small case series in glaucoma, pediatric neuro-ophthalmology, and diabetic retinopathy. RESULTS: A review of well-known ophthalmic case studies by Gass, Irvine, Brockhurst, and others shows that small samples can provide suggestions to the skilled clinician for adding steps to the examination process when uncovering rare or previously unknown associated complications, as is the case for this perspective's initiating studies by Groth and Brodsky. However, as shown by the now-retracted small case series in Lancet connecting measles-mumps-rubella vaccinations with autism, small case series do not replace the value of clinical trials, with rare exception, when considering impacts to widespread, common clinical practice. CONCLUSION: Small case series may contribute to an improved understanding of pathophysiology of rare ophthalmic conditions, but alone are insufficient to provide evidence for changing clinical practice of common eye diseases.

Expansion of Peripheral Visual Field with Novel Virtual Reality Digital Spectacles.

PURPOSE: To examine an image remapping method for peripheral visual field (VF) expansion with novel virtual reality digital spectacles (DSpecs) to improve visual awareness in glaucoma patients. DESIGN: Prospective case series. METHODS: Monocular peripheral VF defects were measured and defined with a head-mounted display diagnostic algorithm. The monocular VF was used to calculate remapping parameters with a customized algorithm to relocate and resize unseen peripheral targets within the remaining VF. The sequence of monocular VF was tested and customized image remapping was carried out in 23 patients with typical glaucomatous defects. Test images demonstrating roads and cars were used to determine increased awareness of peripheral hazards while wearing the DSpecs. Patients' scores in identifying and counting peripheral objects with the remapped images were the main outcome measurements. RESULTS: The diagnostic monocular VF testing algorithm was comparable to standard automated perimetric determination of threshold sensitivity based on point-by-point assessment. Eighteen of 23 patients (78%) could identify safety hazards with the DSpecs that they could not previously. The ability to identify peripheral objects improved with the use of the DSpecs (P = 0.024, chi-square test). Quantification of the number of peripheral objects improved with the DSpecs (P = 0.0026, Wilcoxon rank sum test). CONCLUSIONS: These novel spectacles may enhance peripheral objects awareness by enlarging the functional field of view in glaucoma patients.