SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study.

PURPOSE: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD). METHODS: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual subretinal fluid (SRF) at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52. RESULTS: Enrolled eyes (n = 22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. Best-corrected visual acuity (BCVA) improved significantly from baseline to week 14 (2.52 letters, P < 0.001). The mean central subfield thickness (CST) was also significantly improved at week 14 (-31.9 µ m, P < 0.001) with eight of 22 eyes achieving complete SRF resolution. Only two of eight eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7 µ m compared with week 14. By week 52, improvements in BCVA and CST were lost. CONCLUSION: In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomical improvements during biweekly dosing. These gains, however, were lost on return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.

A Comparison of Peel-Induced Maculopathy Following ILM Peeling Using a Microvacuum Pick Versus Forceps.

OBJECTIVE: To compare peel-induced maculopathy (PIM) using surgical forceps versus the microvacuum pick (MVP). METHODS: Consecutive eyes undergoing internal limiting membrane (ILM) peeling using either the MVP or forceps were assessed. En face optical coherence tomography (OCT) images at the level of the nerve fiber layer were generated for 6-month postoperative visit. The percentage of the imaged area showing PIM was termed the PIM index. PIM severity was additionally measured using a qualitative PIM severity scale. RESULTS: Seventy-four consecutive eyes underwent ILM peeling with either the MVP (36/74; 49%) or forceps (38/74; 51%). At month-6 postoperatively, the mean PIM index for forceps was 7.7% vs 4.7% for the MVP (P < 0.001, R2 = 0.15). At 6 months, 26/38 eyes (68.5%) in the forceps group had either moderate or severe PIM compared to 12/36 eyes (33.3%) in the MVP group (P = 0.001). CONCLUSIONS: ILM peeling with the MVP resulted in lower PIM severity compared to forceps. [Ophthalmic Surg Lasers Imaging Retina 2023;54:37-42.].

BASELINE CHARACTERISTICS OF VITREOMACULAR TRACTION PROGRESSING TO FULL-THICKNESS MACULAR OR LAMELLAR HOLES IN THE PHASE III TRIALS OF ENZYMATIC VITREOLYSIS.

PURPOSE: To identify characteristics associated with progression from vitreomacular traction (VMT) to a full-thickness macular hole (FTMH) or lamellar hole (LH). METHODS: Post-hoc analysis of the Phase III clinical trial comparing ocriplasmin with placebo for treatment of vitreomacular adhesion (MIVI-TRUST). Exact logistic regression analyses were used to identify baseline characteristics significantly associated with progression from vitreomacular traction to FTMH or LH over the 6-month study period. RESULTS: Twenty eyes (4.5%) developed an FTMH and 38 (9.7%) developed an LH during the study period. The rate of progression to FTMH or LH did not differ significantly between ocriplasmin- and saline-treated eyes (P = 0.090 for FTMH, P = 0.369 for LH). On univariate analysis, the presence of subretinal fluid (adjusted odds ratio 5.64, 95% confidence interval 2.02-17.17, P < 0.001) and mean subretinal fluid thickness (adjusted odds ratio 1.10, 95% confidence interval 1.04-1.16, P = 0.003) were associated with FTMH development. Both remained significantly associated with FTMH development on multivariate testing. On univariate analysis, the presence of macular schisis (adjusted odds ratio 2.26, 95% confidence interval 1.30-3.82, P = 0.004) and mean retinal thickness (adjusted odds ratio 1.06, 95% confidence interval 1.01-1.10, P = 0.010) were associated with LH development. Schisis remained a significant predictor of LH formation on multivariate testing. CONCLUSION: Vitreomacular traction is more likely to progress to FTMH when associated with subretinal fluid, but when associated with intraretinal changes (such as schisis), vitreomacular traction appears more likely to progress to a LH after a single intravitreal injection of ocriplasmin or saline.

Reported Complications Following Laser Vitreolysis.

Importance: Use of laser vitreolysis for symptomatic floaters has increased in recent years, but prospective studies are not available and the complication profile is poorly understood. Objective: To analyze cases of complications following laser vitreolysis as voluntarily reported to the American Society of Retina Specialists Research and Safety in Therapeutics (ASRS ReST) Committee, an independent task force formed to monitor device-related and drug-related safety events. Design, Setting, and Participants: A retrospective assessment was performed of all cases of complications following laser vitreolysis that were voluntarily reported by practitioners throughout the United States to the ASRS ReST Committee from the first report on September 19, 2016, through March 16, 2017, the date of data analysis and manuscript writing. Main Outcomes and Measures: Complications reported to the ASRS ReST Committee following laser vitreolysis were analyzed by type to gain an understanding of the spectrum of potential complications. Results: A total of 16 complications following laser vitreolysis were reported in 15 patients by 7 US vitreoretinal specialists during the study period. Complications included elevated intraocular pressure leading to glaucoma; cataracts, including posterior capsule defects requiring cataract surgery; retinal tear; retinal detachment; retinal hemorrhages; scotomas; and an increased number of floaters. Conclusions and Relevance: This report presents a spectrum of complications reported to the ASRS ReST Committee across 6 months. The rate of complications cannot be determined because the denominator of total cases is unknown. Also, these findings cannot determine whether there is a causal association between these complications and laser vitreolysis. Prospective studies are warranted to better understand the efficacy of this procedure and the frequency of attendant complications. Until then, practitioners should be aware of the profile of potential complications to properly inform patients during the consent process. The ASRS ReST Committee will continue to monitor device-related and drug-related adverse events and encourages active surveillance and reporting by all physicians.

A Comparative Study of Rebound Tonometry With Tonopen and Goldmann Applanation Tonometry Following Vitreoretinal Surgery.

PURPOSE: To investigate agreement in intraocular pressure (IOP) measurements among Icare rebound tonometry, Tonopen tonometry, and Goldmann applanation tonometry following vitreoretinal surgery. DESIGN: Reliability analysis of tonometers. METHODS: Fifty-eyes of 50 adults undergoing vitreoretinal surgery were enrolled. IOP was measured on first postoperative day using Icare (Tiolat, Helsinki, Finland), followed by Tonopen (Reichert, Depew, New York, USA) and Goldmann (Haag-Streit USA, Mason, Ohio, USA) in randomized order. Intraclass correlation coefficients (ICC) and Bland-Altman plots were calculated for all subcategories. RESULTS: Icare successfully measured IOP in all eyes, while Goldmann was unmeasurable in 6 eyes (12%) and Tonopen in 1 eye (2%). Mean IOP by Icare, Tonopen, and Goldmann was 15.9 ± 8.9, 16.9 ± 6.2, and 16.0 ± 7.3 mm Hg, respectively (P = .76). Type of intraocular tamponade, status of lens, status of cornea, gauge of instrumentation, and history of prior vitrectomy did not result in significant differences among the 3 tonometers. ICC was excellent (>0.75) in all subgroups, except at IOP <10 and ≥ 23 mm Hg (based on Icare). In eyes with IOP <10 mm Hg, Icare underestimated IOP (mm Hg; P = .01) compared to Goldmann (2.0 ± 2.1) and Tonopen (3.5 ± 2.4), whereas at IOP ≥ 23 mm Hg Icare was overestimated (P = .01) compared to Goldmann (3.77 ± 3.49) and Tonopen (4.97 ± 3.33). Overall, differences in IOP were ≤ 3 mm Hg in 58% of eyes for Icare-Tonopen, 72% for Tonopen-Goldmann, and 62% for Icare-Goldmann. CONCLUSION: IOP measurements using Icare rebound tonometry, Tonopen, and Goldmann tonometry are in excellent agreement following vitreoretinal surgery. However, Icare overestimates at IOP ≥ 23 and underestimates at IOP <10 mm Hg.

Retained Intraocular Perfluoro-n-octane After Valved Cannula Pars Plana Vitrectomy for Retinal Detachment.

BACKGROUND AND OBJECTIVE: To investigate cases of retained intraocular perfluoro-n-octane (PFO) after pars plana vitrectomy (PPV) for retinal detachment (RD). PATIENTS AND METHODS: Retrospective, noncomparative case series of six eyes with retained intraocular PFO after RD repair. Clinical data were supplemented with an experimental silicone eye model. RESULTS: A cluster of six cases of retained intraocular PFO after PPV for RD repair were noted shortly after transitioning to valved cannulas. PFO was noted in the anterior chamber (AC) and/or vitreous and removed with AC paracentesis, AC wash-out, and/or PPV. A silicone eye model demonstrated that PFO levels are maintained anterior to cannula insertion with valved cannulas only. CONCLUSION: The authors hypothesize that anterior PFO fill using valved cannulas can lead to sequestration within the AC, zonules, ciliary sulcus, ciliary teeth, and/or capsular bag. They suggest vigilance in not overfilling PFO, particularly when transitioning to use of valved cannulas, to minimize the risk of intraocular retention.

Reduced fluorescein angiography and fundus photography use in the management of neovascular macular degeneration and macular edema during the past decade.

PURPOSE: We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME). METHODS: Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared. RESULTS: From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME. CONCLUSIONS: Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes.

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

PURPOSE: To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. METHODS: Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. RESULTS: Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. CONCLUSION: The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.

Emerging nonsurgical methods for the treatment of vitreomacular adhesion: a review.

With the dissemination of optical coherence tomography over the past two decades, the role of persistent vitreomacular adhesion (VMA) in the development of numerous macular pathologies - including idiopathic macular hole, vitreomacular traction syndrome, cystoid and diabetic macular edema, neovascularization in diabetic retinopathy and retinal vein occlusion, exudative age-related macular degeneration, and myopic traction maculopathy - has been established. While invasive vitreoretinal procedures have long been utilized to address complications related to these disorders, such an approach is hampered by incomplete vitreoretinal separation and vitreous removal, surgical complications, and high costs. In light of such limitations, investigators have increasingly looked to nonsurgical means for the treatment of persistent pathologic VMA. Chief among these alternative measures is the intravitreal application of pharmacologic agents for the induction of vitreous liquefaction and/or vitreoretinal separation, an approach termed pharmacologic vitreolysis. This article aims to review the available evidence regarding the use of pharmacologic agents in the treatment of VMA-related pathology. In addition, a discussion of vitreous molecular organization and principles of physiologic posterior vitreous detachment is provided to allow for a consideration of vitreolytic agent mode of action and molecular targets.

Lubricant degradation and related wear of a steel pin in lubricated sliding against a steel disc.

In lubricated sliding contacts, components wear out and the lubricating oil ages with time. The present work explores the interactive influence between lubricant aging and component wear. The flat face of a steel pin is slid against a rotating steel disk under near isothermal conditions while the contact is immersed in a reservoir of lubricant (hexadecane). The chemical changes in the oil with time are measured by vibrational spectroscopy and gas chromatography. The corresponding chemistry of the pin surface is recorded using X-ray photoelectron spectroscopy while the morphology of the worn pins; surface and subsurface, are observed using a combination of focused ion beam milling and scanning electron microscopy. When compared to thermal auto-oxidation of the lubricant alone, steel on steel friction and wear are found to accentuate the decomposition of oil and to reduce the beneficial impact of antioxidants. The catalytic action of nascent iron, an outcome of pin wear and disk wear, is shown to contribute to this detrimental effect. Over long periods of sliding, the decomposition products of lubricant aging on their own, as well as in conjunction with their products of reaction with iron, generate a thick tribofilm that is highly protective in terms of friction and wear.