LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.

Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Private equity in ophthalmology: differences between present versus past.

PURPOSE OF REVIEW: The purpose of this review is to examine the differences between the current private equity model in ophthalmology practices and the failed physician practice management companies (PPMC) of the 1990s. RECENT FINDINGS: Over the past 5 years, there has been an accelerating expansion of private equity into ophthalmology. In 2022, there are approximately 1400 ophthalmologists affiliated with one of over 30 private equity-controlled entities and further growth appears likely. This contrasts with the PPMC era that had only a few hundred ophthalmologists across a handful of companies and collapsed within 5 years. The reasons for the failure of PPMC model included inadequate capitalization, limited experience managing ophthalmology practices, failure to grow acquired ophthalmology practices, and misperceptions about the future of healthcare. Current private equity entities are characterized by substantial capital, longer term business plans predicated on individual practice growth, increasing market share, physician controlled clinical care, and integration of physicians into administration and governance. SUMMARY: The current private equity model in ophthalmology continues to expand and presents a reasonable model for ophthalmologists considering a change in practice structure. Although distinctly different from the PPMC model, longer follow-up is required to determine the ultimate impact of private equity upon ophthalmology.

LONG-TERM VISUAL OUTCOMES AND THE TIMING OF SURGICAL REPAIR OF FOVEA-SPLITTING RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments. METHOD: A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair. RESULTS: One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P = <0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P = <0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481). CONCLUSION: We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.

Retinal Complications after Yttrium-Aluminum-Garnet Laser Vitreolysis for Vitreous Floaters.

This is an observational case series of two patients who developed direct retinal damage following neodymium-doped yttrium-aluminum-garnet (YAG) laser treatment for symptomatic vitreous floaters. The first patient developed a vitreous hemorrhage and subsequent branch retinal vein occlusion from laser damage to a major retinal venule. The second patient developed a temporal scotoma from a full-thickness retinal break in the posterior pole requiring laser retinopexy. Direct YAG laser damage to the posterior pole can cause permanent visual deficits. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:610-613.].

FEATURES AND OUTCOMES OF EYES THAT UNDERWENT SURGICAL REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENTS AFTER BEING TREATED FOR ACUTE ENDOPHTHALMITIS.

PURPOSE: To evaluate the etiology, clinical course, and outcomes of eyes that suffered postendophthalmitis rhegmatogenous retinal detachments. METHODS: A retrospective, consecutive case series was conducted of patients managed at Associated Retinal Consultants P.C. from January 2013 to December 2019. Patients were identified as having had endophthalmitis by ICD-9/10 codes. Those with endophthalmitis and/or rhegmatogenous retinal detachment not managed at Associated Retinal Consultants from January were excluded. RESULTS: Charts of 413 patients were reviewed and 19 met inclusion criteria. Incidence of rhegmatogenous retinal detachment following infectious endophthalmitis was 4.6%. The most common inciting events for endophthalmitis was intravitreal injection (9 of 19) and cataract surgery (7 of 19). Fifteen of 19 patients were treated with an injection of intravitreal antibiotics and 4 underwent immediate vitrectomy with antibiotic injection. Biopsy cultures were obtained in 18 of 19 patients and yielded positive growth in 12 (66.7%). Seventeen of the 19 eyes were operable. Final retinal reattachment rate was 88.2% (15 of 17). Mean final logMAR visual acuity was 1.58 (Snellen 20/765). Factors associated with worse final visual acuity after surgical repair included preceding intravitreal injection (P = 0.001), streptococcus species (P = 0.024), presence of proliferative vitreoretinopathy (P = 0.015), and use of silicone oil during primary rhegmatogenous retinal detachment repair (P = 0.010). CONCLUSION: Rhegmatogenous retinal detachments following endophthalmitis occur infrequently. Although most eyes can be repaired surgically, visual outcomes are often poor, particularly in eyes that were infected with streptococcal species and had associated proliferative vitreoretinopathy.

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes.

PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multicenter, interventional, retrospective case-control study. PARTICIPANTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery. MAIN OUTCOME MEASURES: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026). CONCLUSIONS: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.

Predictors of Endophthalmitis after Intravitreal Injection: A Multivariable Analysis Based on Injection Protocol and Povidone Iodine Strength.

PURPOSE: To determine the incidence of endophthalmitis after anti-vascular endothelial growth factor (VEGF) therapy at our institution and to identify potential risk factors for endophthalmitis occurring after injection. DESIGN: Retrospective, single-center cohort study. PARTICIPANTS: All patients who received an intravitreal injection of an anti-VEGF medication between January 1, 2014, and March 31, 2017. METHODS: Current Procedural Terminology and International Classification of Diseases billing codes were used to identify instances of anti-VEGF administration and cases of endophthalmitis. Medical records and injection technique were reviewed carefully in each case. Multivariable logistic regression analysis was performed in a stepwise fashion to determine independent predictors of endophthalmitis based on injection protocol. MAIN OUTCOME MEASURES: Incidence of endophthalmitis after injection and odds of endophthalmitis by injection technique with 95% confidence intervals (CIs). RESULTS: A total of 154 198 anti-VEGF injections were performed during the period of interest, resulting in 58 cases of endophthalmitis (0.038% [1:2659]). After adjustment for confounders, both 2% lidocaine jelly (odds ratio [OR], 11.28; 95% CI, 3.39-37.46; P < 0.001) and 0.5% Tetravisc (Ocusoft, Richmond, TX; OR, 3.95; 95% CI, 1.15-13.50; P = 0.03) use were independent risk factors for endophthalmitis after injection. Lid speculum use, povidone iodine strength (5% vs. 10%), injection location (superior or inferior), conjunctival displacement, use of provider gloves, use of a strict no-talking policy, use of subconjunctival lidocaine, and topical antibiotic use were not statistically significant predictors of endophthalmitis after injection. There was no difference in endophthalmitis rate among the anti-VEGF agents (bevacizumab, ranibizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept). CONCLUSIONS: The incidence of endophthalmitis after anti-VEGF injections is low. Use of lidocaine jelly or Tetravisc may increase the risk of endophthalmitis after injection.

DEXAMETHASONE INTRAVITREAL IMPLANT FOR THE TREATMENT OF RECALCITRANT MACULAR EDEMA AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To investigate the efficacy of the intravitreal dexamethasone implant as the treatment for recalcitrant macular edema after successful rhegmatogenous retinal detachment repair. METHODS: A retrospective review of the medical records was performed on 17 consecutive patients (17 eyes) with recalcitrant macular edema associated with rhegmatogenous retinal detachment repair who were treated with a single or multiple injections of an intravitreal dexamethasone 0.7-mg implant (Ozurdex; Allergan Inc) at two centers. Main outcomes of the study were change in logarithm of the minimum angle of resolution visual acuity, measurement of central foveal thickness, and macular cube volume as measured by spectral domain optical coherence tomography and frequency of complications. RESULTS: The mean age was 67 years (range, 51-78 years). All 17 patients received previous topical therapy and 12 of them had previous administration of intravitreal triamcinolone with persistence of macular edema. Baseline mean best-corrected visual acuity was 20/100 (logarithm of the minimum angle of resolution 0.75; range, 0.18-1.3 ±0.37) in the affected eyes. There was a statistically significant improvement in best-corrected visual acuity at 1 month (P < 0.001) and 3 months (P = 0.01). Mean baseline central foveal thickness was 505 µm, and mean macular cube volume was 10.62 mm. There was a statistically significant decrease in central foveal thickness and macular cube volume at 1 month (505-290 µm, P = 0.013 and 10.62-9.13 mm, P < 0.0001) and 3 months (P = 0.01). All patients developed recurrence of macular edema at 3 months, which required retreatment. The average number of implants was 4 (range, 1-14). No adverse effects such as retinal detachment or endophthalmitis occurred. Two patients experienced an increase in intraocular pressure that was controlled with topical therapy. CONCLUSION: Macular edema that occurs in eyes after successful repair of rhegmatogenous retinal detachment can be chronic and recalcitrant, and may be successfully and safely treated with the dexamethasone intravitreal implant.

Detection of pars plana rupture by ultrasound biomicroscopy after cannula dislodgement during cataract wound hydration.

Ultrasound biomicroscopy (UBM) is a valuable diagnostic modality for imaging anterior ocular structures. Its utility has been well studied in anterior segment, lenticular, and pars plicata pathologies. However, imaging of the pars plana has been seldom described. We present the case of a 66-year-old woman referred for vitreous hemorrhage after expulsive cannula dislodgement into the posterior segment during wound hydration at the end of cataract surgery. B-scan ultrasonography initially detected a very anterior abnormality, but the resolution was insufficient for accurate diagnosis. Subsequent UBM clearly showed rupture of the pars plana and a mild cyclodialysis cleft. To our knowledge, this is the first report of a pars plana rupture detected by ultrasound, which expands the diagnostic capacities and indications for UBM.

Stalagmite-like preretinal inflammatory deposits in vitrectomized eyes with posterior uveitis.

We report a new clinical sign of vitreous inflammation in patients with posterior uveitis: spectral-domain optical coherence tomography identified stalagmite-like, discrete, diffusely distributed, hyperreflective, preretinal deposits in previously vitrectomized eyes of 2 patients during flares of posterior uveitis. The extent of the deposits correlated with disease activity. The underlying primary diseases encountered were necrotizing retinochoroiditis secondary to toxoplasmosis and primary central nervous system lymphoma.

RESOLUTION OF SUBRETINAL FLUID AND OUTER RETINAL CHANGES IN PATIENTS TREATED WITH OCRIPLASMIN.

PURPOSE: To evaluate the aftermarket efficacy of ocriplasmin for vitreomacular adhesion (VMA) and identify the frequency and duration of structural changes on optical coherence tomography. METHODS: The authors conducted a retrospective case series of 36 eyes treated with ocriplasmin for symptomatic VMA at a single center between February 2013 and September 2013. Eyes were evaluated for release of VMA at 1 month postinjection, preinjection adhesion size, postinjection closure of macular hole, presence of subretinal fluid after release of adhesion, size of subretinal fluid, outer retinal structural change, and visual acuity at 1 month, 6 months, and 1 year. RESULTS: Fifteen eyes (42%) had complete release of VMA at 1 month postinjection, and 78% of eyes had closure of the macular hole. Eyes that did not have an epiretinal membrane that had a smaller initial adhesion size and a smaller macular hole size were more likely to have complete release of VMA. Subretinal fluid was present after release in 73.3% of treated eyes, and ellipsoid zone changes were present in 66.7% of treated eyes. At the end of 1 year, complete resolution of subretinal fluid occurred in 87% of treated eyes with only trace subretinal fluid remaining in 2 eyes. Complete resolution of ellipsoid zone changes was found in all eyes. Best-corrected visual acuity improved throughout the first year after treatment. CONCLUSION: Ocriplasmin is effective in the treatment of patients with symptomatic VMA. Results can be improved with patient selection based on specific criteria. Subretinal fluid and ellipsoid zone changes are common after treatment but mostly resolve over 1 year.

Aggressive Surgical Therapy With Early Vitrectomy, Panretinal Photocoagulation, and Silicone Oil Tamponade for Streptococcus mitis Endophthalmitis.

An 87-year-old woman presented with acute, painful vision loss in her right eye after intravitreal injection. Examination disclosed hypopyon and vitritis, as well as discrete inflammatory collections in the vitreous and widespread retinal hemorrhages. The patient underwent vitrectomy with injection of intravitreal antibiotics. Vitreous cultures were positive for Streptococcus mitis, a pathogen associated with severe tissue damage and poor clinical outcomes. Clinical deterioration prompted repeat vitrectomy with silicone oil tamponade and panretinal photocoagulation two weeks later, resulting in more favorable anatomic and visual outcomes. Endophthalmitis caused by exotoxin-producing bacterial species such as S. mitis is often associated with severe vision loss or loss of the eye. Aggressive surgical intervention--prompted by concerning clinical findings and vitreous cultures--may play a role in improving outcomes in these patients.

Occlusive vasculitis due to hyperacute Streptococcus mitis endophthalmitis after intravitreal ranibizumab.

PURPOSE: To report a case of hyperacute Streptococcus mitis endophthalmitis after intravitreal ranibizumab resulting in occlusive vasculitis. METHODS: Retrospective case report with ultra-wide-field color fundoscopic and fluorescein angiographic imaging. RESULTS: An 83-year-old woman received an intravitreal injection of ranibizumab to her right eye and was evaluated the next day (less than 24 hours from the injection) because of acute loss of vision. Her vision had decreased from 20/50 to hand motions in the right eye at the time of reevaluation. Wide-field fundus photography demonstrated pallid optic nerve head edema, generalized vascular attenuation, diffuse vascular sheathing, and scattered large postequatorial intraretinal hemorrhages. Ultra-wide-field fluorescein angiography revealed a severely delayed AV transit time associated with extensive areas of retinal nonperfusion and late retinal vascular leakage consistent with occlusive vasculitis. She underwent immediate pars plana vitrectomy with extensive irrigation of the vitreous cavity and intravitreal injection of antibiotics. In light of a worsening clinical course, she was taken for repeat vitrectomy 1 week later with panretinal endolaser photocoagulation, instillation of silicone oil, and sub-Tenon triamcinolone acetonide. At postoperative month 1, she maintained 20/200 vision with improved retinal perfusion on fluorescein angiography. CONCLUSION: We describe a hyperacute case of S. mitis endophthalmitis after intravitreal injection with ranibizumab, associated with severe occlusive vasculitis on ultra-wide-field fluorescein angiography. Aggressive early surgical intervention may be associated with better outcomes than previously reported.

Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3.

IMPORTANCE: The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina. OBJECTIVE: To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING, PARTICIPANTS: The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye. INTERVENTIONS: In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. MAIN OUTCOMES AND MEASURE: S Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy. CONCLUSION AND RELEVANCE: The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4.

IMPORTANCE: Age-related cataract is a leading cause of visual impairment in the United States. The prevalence of age-related cataract is increasing, with an estimated 30.1 million Americans likely to be affected by 2020. OBJECTIVE: To determine whether daily oral supplementation with lutein/zeaxanthin affects the risk for cataract surgery. DESIGN, SETTING, AND PATIENTS: The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, double-masked clinical trial, enrolled 4203 participants, aged 50 to 85 years, at risk for progression to advanced age-related macular degeneration. INTERVENTIONS: Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10mg/2mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination to evaluate the effects on the primary outcome of progression to advanced age-related macular degeneration. MAIN OUTCOMES AND MEASURES: Cataract surgery was documented at annual study examination with the presence of pseudophakia or aphakia, or reported during telephone calls at 6-month intervals between study visits. Annual best-corrected visual acuity testing was performed. A secondary outcome of AREDS2 was to evaluate the effects of lutein/zeaxanthin on the subsequent need for cataract surgery. RESULTS: A total of 3159 AREDS2 participants were phakic in at least 1 eye and 1389 of 6027 study eyes underwent cataract surgery during the study, with median follow-up of 4.7 years. The 5-year probability of progression to cataract surgery in the no lutein/zeaxanthin group was 24%. For lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratios for progression to cataract surgery was 0.96 (95% CI, 0.84-1.10; P = .54). For participants in the lowest quintile of dietary intake of lutein/zeaxanthin, the hazard ratio comparing lutein/zeaxanthin vs no lutein/zeaxanthin for progression to cataract surgery was 0.68 (95% CI, 0.48-0.96; P = .03). The hazard ratio for 3 or more lines of vision loss was 1.03 (95% CI, 0.93-1.13; P = .61 for lutein/zeaxanthin vs no lutein/zeaxanthin). CONCLUSIONS AND RELEVANCE: Daily supplementation with lutein/zeaxanthin had no statistically significant overall effect on rates of cataract surgery or vision loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes.

PURPOSE: Intravitreal bevacizumab (BV) (Avastin, Genentech Inc., South San Francisco, CA) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full-thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare BV retinal penetration in rabbit eyes with and without an MP-induced PVD. METHODS: Twelve adult rabbits were injected with 0.1 mL (0.4 mg) of MP into the vitreous cavity of 1 eye. One week later, the rabbits were injected with 0.05 mL (1.25 mg) of BV into both eyes. Both eyes of 3 rabbits were harvested at 6 hours, 12 hours, 24 hours, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intraretinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 mL of MP in 1 eye. One week later, both eyes from each rabbit were enucleated, and frozen retinal sections were prepared and analyzed with light microscopy to evaluate histologic damage. RESULTS: Full-thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All the MP-injected eyes exhibited increased antibody labeling in retinas evaluated at 6 hours, 12 hours, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By 3 days after BV injection, all eyes demonstrated decreased antibody labeling compared with earlier periods. At 3 days, 1 rabbit showed increased antibody labeling in the retina of the non-MP-injected eye compared with the contralateral MP-injected eye, and 2 rabbits exhibited similar antibody labeling in both eyes. When compared with control eyes, light microscopy demonstrated normal retinal histologic findings in eyes injected only with MP. CONCLUSION: Increased BV retinal penetration is observed initially in eyes with an MP-induced PVD, and the mechanism is likely multifactorial. By 3 days, retinal penetration is similar in eyes with and without a PVD. Although it is difficult to directly extrapolate to humans, our study suggests that a PVD may alter the retinal penetration of BV.

Repair of primary rhegmatogenous retinal detachment using 25-gauge transconjunctival sutureless vitrectomy.

PURPOSE: : To evaluate the anatomical and visual outcomes of primary rhegmatogenous retinal detachment repairs performed using 25-gauge transconjunctival sutureless vitrectomy. METHODS: : A retrospective, noncomparative interventional case series including 53 consecutive eyes of 52 patients who underwent 25-gauge transconjunctival sutureless vitrectomy to repair primary rhegmatogenous retinal detachment was performed. Variables collected for the study were patient demographics, lens status, preoperative visual acuity, and macular status. Outcome measures included single-operation anatomical success rate, final anatomical success rate, postoperative visual acuity, and surgical complications. RESULTS: : The retina was reattached with a single operation in 39 (74%) of 53 eyes. The final anatomical success rate was 100%. The mean time to redetachment was 72 days (range, 13-334 days). Proliferative vitreoretinopathy (64%) and development of new retinal breaks (43%) were the most common reasons associated with redetachment. Mean visual acuity improved from 20/100 to 20/60 (P = 0.001); 55% of eyes had final vision of 20/40 or better. Three eyes (6%) developed postoperative choroidal hemorrhage. Three eyes (6%) developed visually significant macular pucker that required surgery. No postoperative hypotony or endophthalmitis was observed. CONCLUSIONS: : Repair of primary rhegmatogenous retinal detachments using 25-gauge transconjunctival sutureless vitrectomy resulted in excellent final anatomical success rate and postoperative visual outcomes. However, redetachments due to new tears and/or proliferative vitreoretinopathy resulted in a lower single-operation success rate than those reported with 20-gauge systems.

Pars plana vitrectomy with removal of the internal limiting membrane in the treatment of persistent diabetic macular edema.

PURPOSE: To evaluate the benefit of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) in eyes with diffuse diabetic macular edema refractory to laser photocoagulation. DESIGN: Prospective, consecutive, interventional case series. METHODS: Diabetic patients with biomicroscopic, angiographic, and tomographic evidence of diabetic macular edema persisting for at least 3 months after numerous sessions of macular photocoagulation were evaluated for inclusion. Patients with biomicroscopic evidence of epiretinal membrane or taut posterior hyaloid, previous vitreoretinal surgery, or active proliferative diabetic retinopathy were excluded. The main outcome measures were macular thickness, as measured by optical coherence tomography (OCT) and visual acuity (VA). RESULTS: PPV with ILM removal was performed in 11 eyes of 10 patients (four men, six women; mean age = 58.2 years). Six-month follow-up data were available for 10 eyes (91%). At 6 months postoperatively, central macular thickness had improved by at least 20% in eight of 11 eyes (mean preoperative thickness of 421 mum compared with mean postoperative thickness of 188 mum; P = .007). Mean VA improved from 20/352 to 20/94 at 6 months (P = .002). By the most recent visit (range = 6-20 months postoperatively), VA had improved by at least 2 Snellen lines in 6 of 10 eyes treated with surgery alone. CONCLUSIONS: The early results of this ongoing study suggest that PPV with ILM removal may provide anatomic and visual benefit in some eyes with chronic diabetic macular edema unresponsive or unamenable to additional laser photocoagulation.