Benign Lobular Inner Nuclear Layer Proliferations of the Retina Associated with Congenital Hypertrophy of the Retinal Pigment Epithelium.

PURPOSE: To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms. DESIGN: Retrospective case series. PARTICIPANTS: Four patients from 3 institutions. METHODS: Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing. MAIN OUTCOME MEASURES: Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients. RESULTS: Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months-4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype. CONCLUSIONS: We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Risk of hydroxychloroquine retinopathy in the community.

OBJECTIVES: We aimed to estimate the risk of HCQ retinopathy and its risk factors among incident users in the community. METHODS: Using the Rochester Epidemiology Project, a record-linkage system, a cohort of incident users of HCQ was identified from 27 counties in the American upper Midwest. HCQ retinopathy was defined based on characteristic paracentral automated 10-2 visual field (10-2 AVF) defects and parafoveal retinal photoreceptor layer changes on spectral domain optical coherence tomography. Cumulative incidence rates were estimated adjusting for competing risk of death. Risk factors for HCQ retinopathy were examined using Cox models. RESULTS: The study included 634 incident HCQ users (mean age at initial HCQ use was 53.7 years, 79% females, 91% white). Most common indications for HCQ were RA (57%) and SLE (19%). The average follow-up length was 7.6 years. Eleven patients developed HCQ retinopathy (91% females, 91% white). The majority used HCQ for RA (91%). The cumulative incidence rate at year 5 was 0%, which increased to 3.9% (95% CI 2.0, 7.4) by 10 years. Taking an HCQ dose ≥5 mg/kg was associated with a hazard ratio (HR) of 3.59 (95% CI 1.09, 11.84) compared with lower doses. There was a 48% increase [HR 1.48 (95% CI 1.03, 2.14)] in the risk of HCQ retinopathy for each 100 g of HCQ cumulative dose. CONCLUSION: The risk of HCQ retinopathy at 10 years of use is lower compared with previous prevalence-based estimations. A dose ≥5 mg/kg was associated with higher HCQ retinopathy risk.

EFFECT OF PHYSICIAN FACE MASK USE ON POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To examine the impact of physician face mask use on the rates and outcomes of postinjection endophthalmitis. METHODS: A multicenter retrospective, comparative cohort study comparing endophthalmitis rate and visual acuity of eyes that developed endophthalmitis after antivascular endothelial growth factor injections at Mayo Clinic Rochester (MCR) and at Mayo Clinic Health System sites depending on physician masking. RESULTS: A total of 164,824 injections were performed at MCR and Mayo Clinic Health System sites. Of these, 66,098 injections were in the no mask group and 98,726 injections were in the mask group. Overall, there were no differences in the rates of infectious endophthalmitis in the no mask versus mask cohorts (overall: no mask: 20 cases [0.0303%] vs. mask: 41 cases (0.0415%); P = 0.24; infectious: no mask: 12 cases [0.018%] versus mask: 13 cases [0.0132%]; P = 0.42). At MCR alone, there was a significant reduction in infectious endophthalmitis between the no mask versus mask groups (no mask: 9 cases [0.0297%] versus mask: 2 cases [0.003%]; P < 0.001). Only 2 cases of infectious endophthalmitis occurred at MCR after the face mask policy was implemented (1 in 30,000 injections). At presentation and at 6 months, the average visual acuity was similar for patients who developed endophthalmitis between the no mask versus mask groups. CONCLUSION: Physician face mask use did not affect the rate or outcome of postinjection endophthalmitis. However, there was a significant reduction at MCR after masking along with other quality improvement measures, including performance of injections in a dedicated procedure room and preparation of patients by nurses, that led to a low rate of endophthalmitis.

Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy plays a central role in the management of neovascular age-related macular degeneration (nAMD), diabetic retinal disease (DRD), and retinal venous occlusive disease (RVO). Within clinical trials, rates of systemic serious adverse events (SAEs) after anti-VEGF treatment have been low. However, the comparative systemic safety profile of common anti-VEGF agents remains incompletely understood. The goal of this study was to compare the systemic safety of intravitreal bevacizumab, ranibizumab, and aflibercept in real-world practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Using a large U.S. administrative claims database of commercially insured and Medicare Advantage enrollees, we identified adult cohorts receiving initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018. We included patients with 1 year of insurance coverage before initial treatment. METHODS: We compared predefined systemic outcomes between anti-VEGF agents occurring within 180 days of treatment initiation using propensity score-weighted Cox proportional hazards models. Patients were censored upon treatment with a different anti-VEGF medication or termination of health plan coverage. MAIN OUTCOME MEASURES: Primary outcomes were acute myocardial infarction (MI), acute cerebrovascular disease (CVD), major bleeding, and all-cause hospitalization. RESULTS: A total of 87 844 patients received initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018 (69 007 bevacizumab; 10 895 ranibizumab; 7942 aflibercept). Postinjection 180-day event rates per 100 patients for MI, CVD, major bleeding, and all-cause hospitalization were similar for bevacizumab (0.64, 0.59, 0.34, and 10.41, respectively), ranibizumab (0.62, 0.53, 0.40, and 9.44, respectively), and aflibercept (0.63, 0.60, 0.20, and 9.88, respectively). No differences were identified for the risk of MI, CVD, major bleeding, or all-cause hospitalization when comparing the risk-adjusted effect of treatment initiation with bevacizumab versus ranibizumab (hazard ratio [HR], 0.96 [95% confidence interval {CI}, 0.74-1.25]; HR, 1.04 [95% CI, 0.78-1.38]; HR, 0.85 [95% CI, 0.61-1.19]; HR, 1.03 [95% CI, 0.96-1.10], all P > 0.05), bevacizumab versus aflibercept (HR, 0.95 [95% CI, 0.68-1.33], HR, 0.99 [95% CI, 0.71-1.38], HR, 1.02 [95% CI, 0.60-1.74], HR, 1.01 [95% CI, 0.93-1.10], all P > 0.05), or aflibercept versus ranibizumab (HR, 0.91 [95% CI, 0.62-1.35], HR, 1.12 [95% CI, 0.74-1.69], HR, 0.96 [95% CI, 0.53-1.73], HR, 1.02 [95% CI, 0.92-1.13], all P > 0.05). CONCLUSIONS: We observed no differences in the risk of acute MI, CVD, major bleeding, or all-cause hospitalization after treatment initiation with intravitreal bevacizumab, ranibizumab, or aflibercept during routine clinical practice.

Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

PURPOSE: To determine the relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial. PARTICIPANTS: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. METHODS: Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of ≤-0.5, >-0.5 and <0.5, and ≥0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.05-1.59), 3-step progression (HR, 1.35; 95% CI, 1.05-1.73), and PDR (HR, 1.40; 95% CI, 1.02-1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95% CI, 1.03-1.58; 3-step progression: HR, 1.30; 95% CI, 1.00-1.68; PDR: HR, 1.38; 95% CI, 1.00-1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95% CI, 1.00-1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

Risk of Systemic Adverse Events Associated with Intravitreal Anti-VEGF Therapy for Diabetic Macular Edema in Routine Clinical Practice.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy has become standard of care for the management of diabetic macular edema (DME). The systemic safety profile of this treatment in routine clinical practice remains incompletely understood. We used a large claims database to investigate the risk of systemic serious adverse events (SAEs) in patients receiving anti-VEGF for DME compared with controls treated with macular laser photocoagulation or intravitreal corticosteroid. DESIGN: Retrospective cohort study. PARTICIPANTS: By using a large U.S. insurance database, we identified privately insured and Medicare Advantage patients aged ≥18 years treated with anti-VEGF for DME between January 1, 2006, and December 31, 2015, along with control patients receiving macular laser or corticosteroid. We included patients with 1 year of medical coverage before initial DME treatment. METHODS: We assessed associations between treatment modalities and predefined systemic outcomes using Cox proportional hazards regression. We performed 2 separate comparisons, one between anti-VEGF and macular laser and one between anti-VEGF and corticosteroid. We used inverse propensity score weighting for the first comparison to account for treatment selection bias. For the second, we used 2:1 propensity score matching on demographics, year, and baseline comorbidities because of the smaller number of corticosteroid-treated patients. MAIN OUTCOME MEASURES: Risk of cerebrovascular disease, myocardial infarction, major bleeding, and all-cause hospitalization occurring within 6 months of initial DME treatment as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 23 348 patients receiving treatment for DME met inclusion criteria; 13 365 received macular laser, 9219 received intravitreal anti-VEGF, and 764 received intravitreal corticosteroid as initial treatment. Anti-VEGF pharmacotherapy was not associated with an increased hazard of cerebrovascular disease (HR, 0.96; 95% CI, 0.65-1.41; P = 0.83), major bleeding (HR, 1.23; 95% CI, 0.76-1.99; P = 0.41), or myocardial infarction (HR, 1.03; 95% CI, 0.73-1.44; P = 0.88) when compared with macular laser for DME; however, there was an increased hazard of post-treatment all-cause hospital admission (HR, 1.17; 95% CI, 1.05-1.30; P = 0.01). The rates of all primary systemic SAE outcomes were similar after treatment with anti-VEGF versus corticosteroid (P > 0.05 for all). CONCLUSIONS: We identified no increased risk of cerebrovascular disease, myocardial infarction, or major bleeding within 6 months after intravitreal anti-VEGF pharmacotherapy for the treatment of DME in routine clinical practice. A potential difference in all-cause hospitalization may merit further investigation.

Trends of Anti-Vascular Endothelial Growth Factor Use in Ophthalmology Among Privately Insured and Medicare Advantage Patients.

PURPOSE: To characterize the first 10 years of intravitreal anti-vascular endothelial growth factor (VEGF) medication use for ophthalmic disease, including bevacizumab, ranibizumab, and aflibercept. DESIGN: A retrospective cohort study using administrative claims data from January 1, 2006 to December 31, 2015. SUBJECTS: Total of 124 835 patients 18 years of age or over in the United States. METHODS: OptumLabs Data Warehouse, which includes administrative claims data for over 100 million commercially insured and Medicare Advantage individuals, was used to identify patients receiving intravitreal anti-VEGF injections based on Current Procedural Terminology codes. MAIN OUTCOME MEASURES: Total and annual numbers of intravitreal anti-VEGF injections, as well as injections per 1000 enrolled patients per general category of ophthalmic disease, overall and for each available medication. RESULTS: There were 959 945 anti-VEGF injections among 124 835 patients from 2006 to 2015. Among all injections, 64.6% were of bevacizumab, 22.0% ranibizumab, and 13.4% aflibercept; 62.7% were performed to treat age-related macular degeneration (AMD), 16.1% to treat diabetic retinal diseases (including 0.9% of all injections that were for proliferative diabetic retinopathy), 8.3% to treat retinal vein occlusions, and 12.9% for all other uses. Use of bevacizumab and ranibizumab for AMD plateaued as of 2011/2012 and decreased thereafter (in 2006, 58.8 and 35.3 injections/1000 AMD patients, respectively; in 2015, 294.4 and 100.7 injections/1000), whereas use of aflibercept increased (1.1 injections/1000 AMD patients in 2011 to 183.0 injections/1000 in 2015). Bevacizumab use increased each year for diabetic retinal disease (2.4 injections/1000 patients with diabetic retinal disease in 2009 to 13.6 per 1000 in 2015) while that of ranibizumab initially increased significantly and then declined after 2014 (0.1 in 2009 to 4.0 in 2015). Aflibercept use increased each year in patients with diabetic retinal diseases and retinal vein occlusions (both <0.1 per 1000 retinal vein occlusion patients in 2011, 5.6 and 140.2 in 2015). CONCLUSIONS: Intravitreal injections of anti-VEGF medications increased annually from 2006 to 2015. Bevacizumab was the most common medication used, despite its lacking U.S. Food and Drug Administration approval to treat ophthalmic disease, and AMD was the most common condition treated. Ranibizumab use declined after 2014 while both the absolute and relative use of bevacizumab and aflibercept increased.

OUTCOMES OF AN INTRAVITREAL INJECTION CLINIC.

PURPOSE: To examine the safety outcomes of an intravitreal injection-only clinic where patients needing long-term anti-vascular endothelial growth factor therapy are treated with injections at a predetermined interval for a set number of injections without an accompanying clinic visit. METHODS: This is a retrospective chart review of all patients with exudative macular degeneration treated in an intravitreal injection clinic over a 4-year period. Data on the outcome measures of interest were gathered from electronic medical records. RESULTS: There were 556 patients who received 4,386 injections in the injection-only clinic in a total of 1,524 injection cycles. One hundred six cycles were interrupted. The most common causes for interruption were decreased vision in the injected eye (32), decreased vision in the fellow eye (23), flashing lights (6), pain (5), and irritation in the noninjected eye (2). Of patients who had interruption of the cycle, 32 had a new diagnosis (6 corneal abrasions, 6 exudative age-related macular degeneration in fellow eye). There were six instances of conversion to exudative age-related macular degeneration found in the other eye at a routine follow-up visit following the injection clinic. CONCLUSION: An injection-only clinic may provide a reasonable approach to streamline retina practices to ensure that patients receive timely injections.

SCLEROTOMY LEAKAGE IN TRANSCONJUNCTIVAL SMALL-GAUGE PARS PLANA VITRECTOMY: Effect of Removing the Cannula Over the Light Pipe.

PURPOSE: To determine the effect of cannula removal over the light pipe on the incidence of sclerotomy leakage and to evaluate other factors that may influence the incidence of sclerotomy leaks and hypotony on conclusion of small-gauge transconjunctival pars plana vitrectomy. METHODS: Retrospective, interventional clinical study of consecutive patients who underwent small-gauge transconjunctival pars plana vitrectomy at a single academic center. Eyes were divided into a group in which cannulae were removed over the light pipe (Group L) and a group in which cannulae were simply pulled out (Group N). The primary comparison was the comparison in requirement for suturing of sclerotomies between Groups L and N. RESULTS: Forty-eight eyes of 48 patients were included in the study (Group L: 21 eyes; Group N: 27 eyes). In Group L, 14/42 (33%) superior sclerotomies required suturing compared with 7/54 (13%) sclerotomies in Group N (P = 0.024). Superior sclerotomy leaks were also more common in Group L (28/42, 67%) compared with Group N (23/54, 43%, P = 0.024). Similarly, more eyes had hypotony after cannula removal in Group L (11/21; 52%) compared with Group N (5/27; 19%, P = 0.03). There were no differences in any of these measures when comparing fluid-filled to air- or gas-filled eyes. CONCLUSION: Removing the cannula over the light pipe results in a greater frequency of leaking, including leaking that results in hypotony or that requires suturing. The technique of cannula removal affects the risk of leakage and the risk of requiring suturing of a sclerotomy.

High Variation of Intravitreal Injection Rates and Medicare Anti-Vascular Endothelial Growth Factor Payments per Injection in the United States.

PURPOSE: To estimate geographic variation of intravitreal injection rates and Medicare anti-vascular endothelial growth factor (VEGF) drug costs per injection in aging Americans. DESIGN: Observational cohort study using 2013 Medicare claims database. PARTICIPANTS: United States fee-for-service (FFS) Part B Medicare beneficiaries and their providers. METHODS: Medicare Provider Utilization and Payment Data furnished by the Centers for Medicare and Medicaid Services was used to identify all intravitreal injection claims and anti-VEGF drug claims among FFS Medicare beneficiaries in all 50 states and the District of Columbia in 2013. The rate of FFS Medicare beneficiaries receiving intravitreal injections and the mean Medicare-allowed drug payment per anti-VEGF injection was calculated nationally and for each state. Geographic variations were evaluated by using extremal quotient, coefficient of variation, and systematic component of variance (SCV). MAIN OUTCOME MEASURES: Rate of FFS Medicare Part B beneficiaries receiving intravitreal injections (Current Procedural Terminology [CPT] code, 67028), nationally and by state; mean Medicare-allowed drug payment per anti-VEGF injection (CPT code, 67028; and treatment-specific J-codes, J0178, J2778, J9035, J3490, and J3590) nationally and by state. RESULTS: In 2013, the rate of FFS Medicare beneficiaries receiving intravitreal injections varied widely by 7-fold across states (range by state, 4 per 1000 [Wyoming]-28 per 1000 [Utah]), averaging 19 per 1000 beneficiaries. The mean SCV was 8.5, confirming high nonrandom geographic variation. There were more than 2.1 million anti-VEGF drug claims, totaling more than $2.3 billion in Medicare payments for anti-VEGF agents in 2013. The mean national Medicare drug payment per anti-VEGF injection varied widely by 6.2-fold across states (range by state, $242 [South Carolina]-$1509 [Maine]), averaging $1078 per injection. Nationally, 94% of injections were office based and 6% were facility based. CONCLUSIONS: High variation was observed in intravitreal injection rates and in Medicare drug payments per anti-VEGF injection across the United States in 2013. Identifying factors that contribute to high variation may help the ophthalmology community to optimize further the delivery and use of anti-VEGF agents.

MANAGEMENT OF MYCOBACTERIUM CHELONAE ENDOPHTHALMITIS WITH COMPLETE SURGICAL DEBRIDEMENT.

PURPOSE: To report the clinical course and histopathologic findings of two consecutive patients with resolution of Mycobacterium chelonae endophthalmitis and favorable visual outcomes after complete removal of intraocular implants and lens capsular complexes and prolonged sensitivity-guided combination antibiotic therapy. METHODS: Medical records and histopathologic findings were reviewed for two consecutive patients with M. chelonae endophthalmitis. RESULTS: Two consecutive patients with M. chelonae endophthalmitis had prolonged clinical courses with refractory endophthalmitis before complete removal of intraocular implants and lens capsular complexes. One patient had histopathologic evidence of lens remnant-associated acid-fast bacilli. CONCLUSION: Surgical explantation of intraocular implants and lens capsular complexes appears to play an important role in the management of M. chelonae endophthalmitis, which may be closely associated with crystalline lens remnants.

Oral fluoroquinolones and the incidence of rhegmatogenous retinal detachment and symptomatic retinal breaks: a population-based study.

OBJECTIVE: To examine whether oral fluoroquinolone antibiotics are associated with an increase in subsequent rhegmatogenous retinal detachment and symptomatic retinal breaks in a large population-based cohort. DESIGN: Population-based cohort study. PARTICIPANTS AND CONTROLS: Adult residents of Olmsted County, Minnesota, who were prescribed oral fluoroquinolone medications from January 1, 2003, to June 30, 2011. Comparison cohorts consisted of patients prescribed oral macrolide and ß-lactam antibiotics during the study period. METHODS: Procedure codes were used to identify retinal detachment repair and prophylaxis procedures occurring within 1 year of prescription dates. Travel clinic, pro re nata, and self-treatment prescriptions were excluded. Patients with tractional retinal detachment, previous retinal detachment repair, endophthalmitis, and necrotizing retinitis were excluded, as were those with intraocular surgery or severe head/eye trauma ≤90 days before the procedure. MAIN OUTCOME MEASURES: Rates of retinal detachment repair and prophylaxis procedures within 7, 30, 90, and 365 days of the first prescription were calculated and compared between antibiotic prescription cohorts using chi-square tests. Retinal detachment repair rates also were compared with the expected Olmsted County, Minnesota, rates using the one-sample log-rank test. RESULTS: Oral fluoroquinolones were prescribed for 38,046 patients (macrolide n = 48,074, ß-lactam n = 69,079) during the study period. Retinal detachment repair procedures were performed within 365 days of the first prescription in 0.03% (95% confidence interval [CI], 0.01-0.06) of the fluoroquinolone cohort, 0.02% (95% CI, 0.01-0.03) of the macrolide cohort, and 0.03% (95% CI, 0.02-0.05) of the ß-lactam cohort (P > 0.05). Retinal detachment prophylaxis procedures for symptomatic retinal breaks were performed within 365 days of the first prescription in 0.01% (95% CI, 0.00-0.03) of the fluoroquinolone cohort, 0.02% (95% CI, 0.01-0.04) of the macrolide cohort, and 0.02% (95% CI, 0.01-0.04) of the ß-lactam cohort (P > 0.05). Similar comparisons of treatment rates within 7, 30, and 90 days of the first prescription were all nonsignificant between cohorts. Post-fluoroquinolone retinal detachment repair rates were similar to expected rates (36.8 per 100,000/year vs. 28.8 per 100,000/year for age- and sex-matched historical rates, P = 0.35). CONCLUSIONS: Oral fluoroquinolone use was not associated with an increased risk of rhegmatogenous retinal detachment or symptomatic retinal breaks in this population-based study.

The forbidden touch: mechanical clearing of gas-induced crystalline lens feathering during vitrectomy surgery.

BACKGROUND AND OBJECTIVE: Lens feathering due to intraocular gas may cause significant challenges with intraoperative visualization during posterior segment surgery. Herein, we describe an intraoperative technique for improving posterior segment visualization impacted by lens feathering. METHODS: New technique to improve visualization in vitrectomy from gas-induced cataract. RESULTS: The light pipe is used to gently massage posterior subcapsular lens vacuoles to improve the surgical view intraoperatively. CONCLUSION: We report an effective and efficient technique to improve lens feathering during vitreoretinal surgery without need for cataract extraction.

Metastatic papillary renal cell carcinoma to the retina and vitreous.

Purpose: To describe the presentation, evaluation, and management of vitreoretinal metastasis from papillary renal cell carcinoma. Observations: A 53-year-old woman presented with a six-week history of dark floaters in the right eye. Vitreous veils and white pre-retinal plaques were identified in the posterior pole and extended to a temporal peripheral lesion suggestive of retinal infiltration. Optical coherence tomography revealed clumps of pre-retinal hyper-reflective material in the macula and a large hyper-reflective plaque-like lesion involving the internal limiting membrane in the temporal periphery. Fluorescein angiography demonstrated patchy hyperfluorescence with mild leakage at the temporal lesion and there was no evidence of choroidal involvement on indocyanine green angiography. Vitreoretinal biopsy confirmed the diagnosis of metastatic papillary renal cell carcinoma which spurred further systemic metastatic evaluation. Choroidal metastasis developed 15 months later in the fellow eye highlighting different types of intraocular metastatic spread in the same patient. Conclusions and Importance: This case report illustrates a rare presentation of papillary renal cell carcinoma with metastasis to the retina and vitreous. Ophthalmologists should be aware of the appearance and imaging characteristics of retinal and vitreous metastases, which can be the first presentation of a new or newly metastatic malignancy. These lesions can resemble infectious or inflammatory mimickers and may require biopsy to secure the diagnosis and to guide vision- and life-preserving treatment.

Incidence and sex differences of diabetes among youth: a 50-year population-based cohort study.

AIMS: Although the literature on childhood diabetes has traditionally focused on Type 1 diabetes (T1D), youth-onset Type 2 diabetes (T2D) and its associated morbidities have become increasingly prevalent. This study reports on the incidence and demographics of a population-based cohort of children diagnosed with diabetes over a 50-year period. METHODS: Medical records of patients < 22 years diagnosed with diabetes from January 1, 1970, through December 31, 2019, were retrospectively reviewed using the Rochester Epidemiology Project, a database of clinics and hospitals in Olmsted County, Minnesota. RESULTS: Of 606 children diagnosed with diabetes, 519 (85.6%) were diagnosed with T1D at a mean age of 10.9 ± 5.3 years. 87 (14.4%) were diagnosed with T2D at a mean age of 17.4 ± 3.4 years. The incidence of T2D increased 23-fold (p < 0.001) over the five-decade period (5 per 100,000 children/year) while T1D remained stable (26 per 100,000 children/year; p = 0.08). The mean body mass index at T2D diagnosis (35.5 kg/m2 ± 10.4) was significantly higher than in T1D (18.9 kg/m2 ± 4.6 [95% CI for difference 14.2-19.0]; p < 0.0001). Sixty-nine percent of children diagnosed with T2D were female, and the hazard ratio of developing diabetic retinopathy in females with T2D compared to males was 6.83 (95% CI 1.53-30.44; p = 0.012). CONCLUSIONS: The incidence of youth-onset T2D increased significantly over the 50-year period while the incidence of T1D remained stable. A higher proportion of females were diagnosed with youth-onset T2D. Females with T2D were more than six times likelier to develop diabetic retinopathy than males.

The Effect of Scleral Buckle Surgery on Tonographic Outflow Facility, Positional Intraocular Pressure, and Ocular Biomechanics.

PURPOSE: To investigate the in vivo effect of scleral buckle surgery on ocular biomechanics and aqueous humor dynamics. DESIGN: Prospective observational cross-sectional study. PARTICIPANTS: Nine patients with unilateral 360 degree encircling scleral buckles without vitrectomy for rhegmatogenous retinal detachments, between 3 and 39 months postoperative. METHODS: All measurements were performed in both eyes of all participants. Intraocular pressure (IOP) was measured in the seated and supine positions using pneumatonometry. Outflow facility was measured using 2-minute weighted pneumatonography. Ocular rigidity coefficient was determined from the Friedenwald equations based on the difference in IOP with and without a weighted tonometer tip. The percentage change in IOP upon transitioning from seated to supine was calculated. Measurements for buckled and nonbuckled eyes were compared using paired Student t test of means. MAIN OUTCOME MEASURES: Sitting and supine IOP and percentage difference between the 2 positions; outflow facility; ocular rigidity coefficient. RESULTS: Seated IOP was similar between buckled and nonbuckled eyes (16.1 ± 2.5 vs. 16.7 ± 2.7 mmHg; P = 0.5) whereas supine IOP was lower in buckled eyes compared with nonbuckled eyes (18.7 ± 2.6 vs. 21.3 ± 2.5 mmHg; P = 0.008). The percentage increase in IOP upon change in body position from seated to supine was greater in nonbuckled eyes (17.4 ± 9.4% vs. 27.6 ± 9.5%; P = 0.005). Ocular rigidity coefficient was lower in buckled (9.9 × 10-3 ± 1.4 × 10-3 µL-1) vs. nonbuckled eyes (14.4 × 10-3 ± 3.1 × 10-3 µL-1; P = 0.006). Outflow facility was not significantly different in buckled and nonbuckled eyes. CONCLUSIONS: Scleral buckling decreases ocular rigidity but does not affect outflow facility. This change in ocular biomechanics likely results in the attenuated IOP change from seated to supine position. Decreased ocular rigidity may also reduce IOP fluctuations and potentially reduce the risk for glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy.

OBJECTIVE: To investigate whether the choice of glucose-lowering agent for type 2 diabetes (T2D) impacts a patient's risk of developing sight-threatening diabetic retinopathy complications. DESIGN: Retrospective observational database study emulating an idealized target trial. SUBJECTS: Adult (≥21 years) enrollees in United States commercial, Medicare Advantage, and Medicare fee-for-service plans from January 1, 2014, to December 31, 2021, with T2D and moderate cardiovascular disease (CVD) risk who had no baseline history of advanced diabetic retinal complications, initiating treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas. METHODS: We used inverse propensity scoring weights in time-to-event Cox proportional hazards models. MAIN OUTCOME MEASURES: Treatment for either diabetic macular edema or proliferative diabetic retinopathy. RESULTS: The final study population included 371 698 patients, of whom 42 265 initiated GLP-1 RA, 53 476 initiated SGLT2i, 78 444 initiated DPP-4i, and 197 513 initiated sulfonylurea agents. The probability of treatment for sight-threatening retinopathy within 2 and 5 years was 0.3% and 0.7% for patients initiating SGLT2i (median follow-up 830 [interquartile range (IQR), 343-1401] days), 0.4% and 1.0% for GLP-1 RA (669 [IQR, 256-1167] days), 0.4% and 0.9% for DPP-4i (1263 [IQR, 688-1938] days), and 0.5% and 1.2% for sulfonylurea (1223 [IQR, 662-1879] days). Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of treatment for sight-threatening retinopathy compared with all other medication classes, including GLP-1 RA (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97), DPP-4i (HR, 0.79; 95% CI, 0.64-0.97), and sulfonylurea (HR, 0.61; 95% CI, 0.50-0.74). Glucagon-like peptide-1 receptor agonists use was associated with a similar risk of sight-threatening retinopathy as DPP-4i (HR, 1.07; 95% CI, 0.85-1.35) and sulfonylurea (HR, 0.83; 95% CI, 0.67-1.03). CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of sight-threatening diabetic retinopathy among adults with T2D and moderate CVD risk compared with other glucose-lowering therapies. Glucagon-like peptide-1 receptor agonists do not confer increased retinal risk, relative to DPP-4i and sulfonylurea medications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcomes of Hyperbaric Oxygen Treatment for Central Retinal Artery Occlusion: A Single Center Experience.

PURPOSE: To describe the outcomes of hyperbaric oxygen therapy (HBOT) for patients with central retinal artery occlusion (CRAO) at a single tertiary care center. DESIGN: Retrospective clinical cohort study. METHODS: Medical records of all patients diagnosed with CRAO who received HBOT at Mayo Clinic in Rochester, Minnesota from 1/1/2009 to 12/31/2020 were reviewed to confirm diagnosis, time from onset to presentation, exam findings, treatments, and follow-up data. Main outcome measures included final visual acuity (VA) and number of lines of improvement. RESULTS: There were 41 patients diagnosed with CRAO who received HBOT during the 12 year study period. Median time from symptom onset to HBOT treatment was 9.5 hours (interquartile range [IQR] 6.5, 14.0 hours), and patients received a median of 4 HBOT sessions (IQR 2.5, 6.0 sessions). There were 20 patients who received HBOT within 9 hours, 14 (70%) of which had clinically meaningful improvement in VA of ≥0.3 logMAR. In comparison, of the 21 patients treated after 9 hours, 6 (28.6%) had VA improvement of ≥0.3 logMAR (p=0.008). For all patients, the median logMAR VA at presentation was 2.00 (IQR 1.70, 2.30) and the median logMAR VA at follow-up was 1.94 (IQR 1.00, 2.00) (p<0.001), with median lines of improvement of 3.0 (IQR 0.0, 7.0). For patients treated within 9 hours, the median logMAR VA at presentation was 2.00 (IQR 1.93, 2.30) and the median logMAR VA at follow-up was 1.70 (IQR 0.54, 2.00). Patients treated within 9 hours had statistically significant greater median lines of VA improvement than cases that were treated after >9 hours from symptom onset at 5.9 (IQR 3.0, 10.0) and 0.0 (IQR 0.0, 3.0), respectively (p<0.001). There was no difference in VA recovery associated with specific retinal exam findings such as cherry-red spot (p=0.22) and cilioretinal artery perfusion (p=0.36) compared to patients without those findings. CONCLUSION: There was a statistically significant improvement in VA after HBOT treatment in CRAO patients among patients that received early HBOT, with patients receiving the most benefit when receiving treatment within 9 hours. Randomized control trials in patients with CRAO are required to confirm the efficacy of HBOT.

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone.

Objective: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. Design: Randomized, masked multicenter study. Participants: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. Methods: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). Main Outcome: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. Results: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy (P < 0.001, P < 0.001) between LLM, Expert and Expert + AI groups. For quality, Expert + AI (3.86 ± 0.85) performed the best overall while GPT-3.5 (3.75 ± 0.79) was the top performing LLM. For empathy, GPT-3.5 (3.75 ± 0.69) had the highest mean score followed by Expert + AI (3.73 ± 0.63). By mean score, Expert placed 4 out of 7 for quality and 6 out of 7 for empathy. For both quality (P < 0.001) and empathy (P < 0.001), expert-edited LLM responses performed better than expert-created responses. There were time savings for an expert-edited LLM response versus expert-created response (P = 0.02). ChatGPT-4 performed similar to Expert for inappropriate content (P = 0.35), missing content (P = 0.001), extent of possible harm (P = 0.356), and likelihood of possible harm (P = 0.129). Conclusions: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article.