Mean Improvement In Visual Acuity Research Articles

Title - Long term outcomes of vitrectomy and ERM peel: Can pre-operative metamorphopsia measured using the D-Chart help improve surgical candidate selection?

To assess the predictive value of pre-operative metamorphopsia, measured using the D-Chart, in patients undergoing epiretinal membrane (ERM) surgery and how this relates to improvement in quality of life after surgery. 17 patients from vitreo-retinal surgery clinics at a tertiary ophthalmology centre were recruited when listed for pars plana vitrectomy (PPV) with ERM peel between September 2019 - February 2020. Pre-operatively patients underwent visual acuity (VA), Visual-Function Index 14 (VF-14) and metamorphopsia (D-Chart-Thomson Software Solutions) assessment and answered a questionnaire regarding cardinal ERM symptoms. Post-operatively patients were re-assessed in the same domains. 13 patients completed the protocol (inclusion rate 76%) with a mean follow-up of 32.1 (± 3.1) months. Mean pre-operative VA of the affected eye was 0.42 logMAR (± 0.25). Mean pre-operative VF-14 score was 81.51 (± 12.8) and mean M-Score of the affected eye was 14.6 (± 12.7). Post-operatively, mean VA of the operated eye was 0.11 logMAR (± 0.11), mean VF-14 score was 97.4 (± 3.8) and mean M-Score was 1.31 (± 2.8). Mean improvement in VA was 0.31 logMAR (p < 0.001), in VF-14 15.9 (p = 0.002), and M-Score -13.3 (p = 0.003). There was a significant association between pre-operative D-Chart score and improvement in VA (r = -0.570, p = 0.042), visual functioning (r = 0.606 p = 0.028) and metamorphopsia (r = 0.916 p < 0.001), with those demonstrating poorer D-Chart scores showing greater improvements. Pre- and post-operative visual distortion measured using the D-Chart, correlates with vision related quality of life in patients undergoing epiretinal membrane surgery. Patients with worse pre-operative distortion scores noticed the greatest improvements in distortion and vision related quality of life following surgery. With a mean follow-up time of 32.1 months, this long-term follow-up data further reinforces the efficacy of vitrectomy and ERM peel by demonstrating significant and sustained improvement in visual acuity, metamorphopsia and visual functioning. The authors suggest there is a role for D-Chart assessment pre-operatively to improve selection of patients in ERM surgery.

Nonpenetrating Foldable Intrastromal Keratoprosthesis: A Review of the Literature.

To review the literature focusing on the clinical outcomes of KeraKlear (KK) (KeraMed), a foldable intrastromal keratoprosthesis. We searched 6 databases using 4 keywords: KeraKlear, Foldable Keratoprosthesis, Intrastromal Keratoprosthesis, and Non-penetrating Keratoprosthesis. Included studies had to be conducted in vivo on humans, published until January 3, 2023, and had to investigate the implantation of the KK. Eyes were considered at high risk of keratoprosthesis retention failure whenever there was an active inflammatory ocular surface disorder or in case of previous KK failure. We aimed at recording the postoperative complications, rate of prosthesis retention, and mean improvements in visual acuity. We identified 144 publications, 6 of which (38 eyes) met the inclusion criteria. No randomized controlled trials were found, and some studies had significant limitations regarding sample size and follow-up duration. With a mean follow-up of 28 ± 18.8 months, postoperative complications of any kind occurred between 0% and 50% and 24% had an implant extrusion/needed a reoperation. The mean postoperative visual acuity improvement on the last follow-up was -0.83 ± 0.27 LogMAR, that is, -0.57 ± 0.3 for high-risk and -1.03 ± 0.25 for low-risk eyes, whereas 1 year after implantation, 50% of the prostheses were retained in the former and 81% in the latter group. None of the eyes developed glaucoma, endophthalmitis, or expulsive hemorrhages; none had to be eviscerated/enucleated. Despite the limited quality and quantity of evidence, the available literature seems to suggest the KK to be a valuable tool in the treatment of complicated corneal disorders. Because in many parts of the world, the access to corneal transplantation is limited, this prosthesis could represent a valid alternative.

A Remote Consult Retinal Artery Occlusion Diagnostic Protocol

To report a novel protocol for diagnosis of retinal artery occlusions at the point of care using OCT and a remote consult model. Retrospective case series and evaluation of a diagnostic test or technology. Adult patients who presented with painless monocular vision loss and were diagnosed with a nonarteritic retinal artery occlusion. OCT machines were placed in the stroke center or emergency department at 3 hospitals within our health system. Patients who presented with painless monocular vision loss were evaluated by the stroke neurology service and an OCT was acquired. The images were interpreted remotely by the retina service. An in-house ophthalmology consult was not required to make the final treatment decision. Eligible patients were treated with intra-arterial tissue plasminogen activator (IA-tPA). Patients were followed by ophthalmology during their admission when an in-house consultation service was available or otherwise evaluated immediately after discharge. Visual acuity (VA) before and after treatment with IA-tPA; time from last known well (LKW) to treatment; and time from presentation to treatment. In the first 18 months since the protocol went live, 59 patients were evaluated. Twenty-five patients (42%) had a confirmed retinal artery occlusion based on OCT and follow-up examination. Ten patients were eligible for treatment, and 9 patients received treatment with IA-tPA. There was a statistically significant improvement in mean VA from logarithm of the minimum angle of resolution (logMAR) 2.14 to logMAR 0.7 within 24 hours after treatment (P= 0.0001) and logMAR 1.04 after 4 weeks (P= 0.01). Clinically significant improvement was noted in 66% of patients within 24 hours and maintained through 1 month in 56% of all treated patients. The mean time to treatment from LKW was 543 minutes and from presentation at the stroke center was 146 minutes. We report the successful implementation of a remote consult protocol using point-of-care automated OCT. This novel paradigm demonstrates the potential utility of remote consult services for the diagnosis of time-sensitive ophthalmic emergencies. Proprietary or commercial disclosure may be found after the references.

Impact of Anti-VEGF Treatment and Patient Characteristics on Vision Outcomes in Neovascular Age-related Macular Degeneration: Up to 6-Year Analysis of the AAO IRIS® Registry

To evaluate anti-VEGF treatment patterns and the influence of patient demographic and clinical characteristics on up to 6-year vision outcomes in neovascular age-related macular degeneration. Retrospective, multicenter, noninterventional registry study with up to 6 years of follow-up. A cohort of 254 655 eyes (226 767 patients) with first anti-VEGF injection and at least 2 years of follow-up; 160 423 eyes had visual acuity (VA) data. Anonymized patient data were collected in the United States through the IRIS® Registry (Intelligent Research in Sight). Changes in VA from baseline; frequency of and gaps between intravitreal anti-VEGF injections; treatment discontinuations; switching anti-VEGF agents; and influence of baseline clinical and demographic characteristics on VA. After a mean VA increase of 3.0 ETDRS letters at year 1, annual decreases led to a net loss from baseline of 4.6 letters after 6 years. Patients with longer follow-ups had better baseline and follow-up VA. From a mean of 7.2 in year 1 and 5.6 in year 2, mean injections plateaued between 4.2 to 4.6 in years 3 through 6. Treatment was discontinued in 38.8% of eyes and switched in 32.3%. When adjusting for differences at baseline, every additional injection resulted in a 0.68 letter improvement from baseline to year 1; thus, multiple injections in a year have the potential to be clinically meaningful. Older age, male gender, Medicaid insurance, and not being treated by a retina specialist were associated with a higher likelihood of vision loss at year 1. Of the patients, 58.5% lost ≥ 10 letters VA at least once during follow-up, with 14.5% of patients experiencing sustained poor vision after a median of 3.4 years. After modest mean VA improvement with intravitreal anti-VEGF injections at year 1, patients netted a loss of VA by year 6. Injection frequency decreased over time, and this was paired with a relatively high rate of discontinuation. Modeling suggested that more frequent injections were associated with better VA. Difficulty with continuous adherence to frequent intravitreal injections may have contributed to undertreatment resulting in less-than-optimal vision outcomes. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Surgical management of dysthyroid optic neuropathy: A systematic review

ObjectiveThere is currently no recommendation on the optimal surgical management for dysthyroid optic neuropathy (DON). The aim of this study is to systematically review the surgical management of DON and its outcome on visual acuity (VA). Data sourcesMEDLINE, Cochrane Library, and clinicaltrials.gov Review MethodsA systematic review of studies about the surgical management of DON was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were included if preoperative and postoperative VA in logMAR (Logarithm of the Minimum Angle of Resolution) were available. ResultsFifteen articles were included in the study accounting for 669 orbits. The mean VA improvement was of 0.44 logMAR overall, 0.41 logMAR for 1-wall, 0.41 logMAR for 2-wall, and 0.55 logMAR for 3-wall decompressions. The mean reduction in exophthalmos was 4.9 mm overall, 4.3 mm for 1-wall, 4.54 mm for 2-wall, and 6.02 for 3-wall decompressions. The mean new onset diplopia (NOD) rate was 19.84% overall, 19,12% for 1-wall, 20.75% for 2-wall, and 19.83% for 3-wall decompressions. ConclusionThe results are limited due to the high number of biases in the included studies. It seems that 3-wall decompression offers the best VA improvement and proptosis reduction although also the highest NOD and complications rate. Two-wall balanced decompression or 1-wall inferomedial decompression seems to be effective with less morbidity.

Real world outcomes of photodynamic therapy for chronic central serous chorioretinopathy

ObjectivesWe describe the real-world outcomes of photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR) in a single centre over nine years.MethodsWe carried out a retrospective analysis of patients with chronic CSCR who received half dose PDT in a single centre between 2011 and 2019. Visual acuity (VA) and retinal thickness (RT) was recorded between baseline visit and first recorded review visit.ResultsWe included 125 eyes of 113 patients in this study. Mean age at treatment was 55.0 ± 12.1 years, with a higher male predominance (83 men, 30 women). Mean baseline VA was 0.40 ± 0.31 logMAR with a mean visual outcome gain post-PDT of 0.05 logMAR (p = 0.005). Mean baseline RT was 390 ± 82 microns with a mean reduction of RT post-PDT of 66 microns (p < 0.001). 17.6% of eyes were treated for recurrent CSCR.ConclusionWe found overall a mean improvement in VA and structural outcomes after PDT. In the absence of randomised clinical trials this study supports the use of half dose PDT for treatment of chronic CSCR.

Six-month outcomes of infliximab and tocilizumab therapy in non-infectious retinal vasculitis.

To evaluate the efficacy of infliximab (IFX, 5-10 mg/kg) (Group 1) and tocilizumab (TCZ, 4-8 mg/kg) (Group 2) infusions in non-infectious retinal vasculitis (RV) using Angiographic Scoring for the Uveitis Working Group fluorescein angiography (FA) scoring system. Records of 14 patients (24 eyes) in Group 1 and 8 patients (11 eyes) in Group 2 were retrospectively evaluated to assess visual acuity (VA), anterior chamber cell and flare, vitreous haze, central subfield thickness (CST), and FA scoring at baseline and 6 months of follow-up. The measurements were employed to grade in each group. In Group 1 and 2, respectively, there was no underlying disease in 9 (60%) and 3 (42.9%) patients. Three (42.9%) patients in Group 2 had juvenile idiopathic arthritis (JIA) as the most common identified cause. Mean improvement in VA (log MAR) and CST were 0.04 ± 0.14 and 40.3 ± 78.5 µm in Group 1; 0.04 ± 0.09 and 47.3 ± 82.3 µm in Group 2, respectively. Mean FA scores were significantly reduced from 12.4 ± 5.2 and 11.6 ± 4.4 at baseline to 6.4 ± 5.0 and 5.8 ± 3.9 at 6-month in Group 1 and 2, respectively. In Group 2, 9 eyes of 6 patients (75%) had the history of IFX use prior to TCZ initiation. There was no significant safety concern requiring treatment discontinuation during the follow-up in either group. IFX and TCZ infusions showed statistically significant improvement of non-infectious RV as shown by ASUWOG FA Scoring System. TCZ, as well as IFX, appeared to be effective treatment options for non-infectious RV.

Predictors of visual acuity improvement after phacoemulsification cataract surgery.

PurposeThis study aimed to assess preoperative predictors of visual outcome after phacoemulsification cataract surgery in Jordan, a Middle Eastern country.MethodsThis was a retrospective longitudinal study of adult patients who underwent phacoemulsification cataract surgery from January 2019 to July 2021. For each patient, we included only the first operated eye. We obtained pre-operative ocular history, cataract surgery complication risk based on a predesigned score, visual acuity, best correction, and best corrected visual acuity. We recorded intraoperative complications. We also obtained postoperative best corrected visual acuity and refractive error for correction after 1–3 months.ResultsA total of 1,370 patients were included in this study, with a mean age of 66.39 (± 9.48). 48.4% of patients achieved visual acuity ≥ 0.8, and 72.7% achieved visual acuity ≥ 0.5. The mean visual acuity improvement after phacoemulsification cataract surgery was 0.33 (95% CI 0.31–0.35). In the regression model, significant predictors that affected visual acuity improvement included the presence of diabetic retinopathy, glaucoma, and complication risk factors (i.e., high-risk surgery).ConclusionPredictors of visual acuity improvement vary between studies. This study was conducted in a developing country; we defined predictors of visual acuity improvement. We also provided a new preoperative phacoemulsification cataract surgery complication risk score.

Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema

BackgroundIn eyes with diabetic macular edema, the relative efficacy of administering aflibercept monotherapy as compared with bevacizumab first with a switch to aflibercept if the eye condition does not improve sufficiently (a form of step therapy) is unclear.MethodsAt 54 clinical sites, we randomly assigned eyes in adults who had diabetic macular edema involving the macular center and a visual-acuity letter score of 24 to 69 (on a scale from 0 to 100, with higher scores indicating better visual acuity; Snellen equivalent, 20/320 to 20/50) to receive either 2.0 mg of intravitreous aflibercept or 1.25 mg of intravitreous bevacizumab. The drug was administered at randomization and thereafter according to the prespecified retreatment protocol. Beginning at 12 weeks, eyes in the bevacizumab-first group were switched to aflibercept therapy if protocol-specified criteria were met. The primary outcome was the mean change in visual acuity over the 2-year trial period. Retinal central subfield thickness and visual acuity at 2 years and safety were also assessed.ResultsA total of 312 eyes (in 270 adults) underwent randomization; 158 eyes were assigned to receive aflibercept monotherapy and 154 to receive bevacizumab first. Over the 2-year period, 70% of the eyes in the bevacizumab-first group were switched to aflibercept therapy. The mean improvement in visual acuity was 15.0 letters in the aflibercept-monotherapy group and 14.0 letters in the bevacizumab-first group (adjusted difference, 0.8 letters; 95% confidence interval, −0.9 to 2.5; P=0.37). At 2 years, the mean changes in visual acuity and retinal central subfield thickness were similar in the two groups. Serious adverse events (in 52% of the patients in the aflibercept-monotherapy group and in 36% of those in the bevacizumab-first group) and hospitalizations for adverse events (in 48% and 32%, respectively) were more common in the aflibercept-monotherapy group.ConclusionsIn this trial of treatment of moderate vision loss due to diabetic macular edema involving the center of the macula, we found no evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response. (Funded by the National Institutes of Health; Protocol AC ClinicalTrials.gov number, NCT03321513.)

Effectiveness of syntonic phototherapy in amblyopia in terms of improved visual acuity and contrast sensitivity

Purpose: To compare visual acuity and contrast sensitivity in different types of amblyopia and to see the effect of syntonic therapy on amblyopia in terms of visual acuity and contrast sensitivity. Study Design: A Quasi Experimental study Place and Duration of Study: A Qusai Experimental study was carried out from August 2021 to November 2021 at Madina Teaching Hospital Faisalabad. Methods: A total of 30 patients of either gender and age from 8 to 18 years were included. There were 15 patients with anisometropic amblyopia and 15 with strabismic amblyopia. The patients were recruited through non-probability purposive sampling technique. All the patients underwent assessment of visual acuity with Log MAR chart and contrast sensitivity with Pelli-Robsonchart. Syntonic phototherapy with red filter glasses was prescribed for 4 weeks. After 4 weeks, patients returned and underwent post-therapy assessment of visual acuity and contrast sensitivity. Paired sample t test and Independent sample t test was used with the help of IBM SPSS-23 to get a statistical result. Results: Syntonic phototherapy showed significant improvement in mean visual acuity of 0.223 (p=0.00) and contrast sensitivity of -0.200 (p=0.00) in amblyopia. Anisometropic amblyopia showed better improvement in visual acuity (p=0.016) and contrast sensitivity (p=0.035) by syntonic phototherapy as compared to patients with strabismic amblyopia. Conclusion: Significant improvement was seen in visual acuity and contrast sensitivity in patients with amblyopia after syntonic phototherapy. Anisometropic amblyopia showed better improvement as compared to strabismic amblyopia, in terms of visual acuity and contrast sensitivity.

45-OR: Less Favorable Response to Anti-VEGF Therapy in Patients with Diabetic Macular Edema and Decreased Baseline Outer Retinal Layer Thickness

Early identification of patients who are more likely to respond to anti-VEGF therapy for diabetic macular edema (DME) would improve patient management and allow for more rapid assessment of new therapeutic targets. This study evaluated retinal thickness variables and their association with anti-VEGF therapy response in patients with DME. We identified patients at the Joslin Diabetes Center who received their first anti-VEGF injection for DME between 1/2016-12/20 and assessed mean change in visual acuity (VA) and central retinal thickness (RT) at 6 mos. A good VA or RT response to anti-VEGF therapy was defined using thresholds of letter and retinal thickness change as follows: eyes with baseline VA of ≥20/32, ≥5 letters; 20/40-20/70, ≥letters; ≤20/80, ≥15 letters and eyes with baseline RT of &amp;lt;375µm, &amp;gt;10%; 375-449µm, &amp;gt;20%; &amp;gt;449µm, &amp;gt;25%. A total of 151 eyes from 126 patients fell into the following responder groups: both VA and RT response (32.5%) , only VA response (21.9%) or RT response (11.3%) , and neither VA nor RT response (34.4%) , with 57.0% of all eyes exhibiting VA response and 43.7% exhibiting RT response. While diabetes duration, A1c, and blood pressure were not associated with responder group, decreased baseline thickness of the outer retinal layer (ORL) was more likely to be present in eyes with neither VA nor RT response (β=-.018; 95% CI -0.03 to -0.01; P=.006) . Improvement in mean VA was associated with younger age (β=.004; 95% CI 0.001-0.007; P=.01) . Decreased baseline ORL thickness (β=-.003; 95% CI -0.0to -0.001; P=.01) and increased baseline inner retinal layer (IRL) thickness (β=.0004; 95% CI 0.0001-0.0007; P=.02) were associated with less VA gain at 6 mos. These findings suggest that decreased baseline ORL thickness is associated with less favorable outcome after anti-VEGF therapy and may be a potential biomarker for treatment response in patients with DME. Disclosure M.G.Mitzner: None. W.Fickweiler: None. D.B.Robinson: None. T.Boumenna: None. L.P.Aiello: Consultant; KalVista Pharmaceuticals, Inc., Novo Nordisk, Stock/Shareholder; KalVista Pharmaceuticals, Inc. J.Sun: Consultant; American Diabetes Association, American Medical Association, Research Support; Adaptive Sensory Technology, Boehringer Ingelheim International GmbH, Genentech, Inc., Jaeb Center for Health Research, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Optovue, Incorporated, Physical Sciences, Inc, Roche Pharmaceuticals. Funding American Diabetes Association (7-21-PDF-022) ; National Eye Institute (R01EYE26080-01) ; National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3-DK-094333-01) ; JDRF (17-2013-310) ; The Dianne Nunnally Hoppes Fund; The Beatson Pledge Fund

A hospital-based observational comparative study of efficacy of intracameral voriconazole and oral ketoconazole in deep keratomycosis

Background: Fungal keratitis, one of the most common causes of ocular mycosis, is the second most common cause of blindness in the world, after cataracts. The aim of the study was to compare the efficacy of conventional topical, systemic medications and intracameral voriconazole injection in visual and structural outcomes in keratomycosis. Material and methods: We conducted a hospital-based observational study of 45 patients of 45 eyes with smear-positive fungal keratitis. Patients were categorized into three groups: Group I received systemic topical with oral ketoconazole 200 mg, Group II — topical medications with intracameral voriconazole 50 μgm/0.1 mL, Group III — topical medications with both oral ketoconazole 200 mg and intracameral voriconazole 50 μgm/0.1 mL. Results: The common fungal organism is identified as Fusarium. The mean final visual acuity (VA) was 1.25 ± 0.32, 1.47 ± 1.05, and 1.22 ± 0.37 logMAR in Group I, group II, and Group III, respectively. The mean improvement in VA was 0.33 ± 0.07, 0.01 ± 0.71, and –0.19 ± 0.02 logMAR without significant change (p = 0.9). There was a significant difference in VA between the final postoperative follow-up period and baseline in Group I cases (p = 0.0019). Whereas no difference in VA between the final postoperative follow-up period and baseline in either Group II (p = 0.0671) or Group III (p = 0.1505) cases. The difference in time between the disappearance of hypopyon and the mean time to infection healing was not statistically significant (p = 0.1). Three cases in each group were perforated, and keratoplasty was performed. These perforated cases did not show culture positive. Histopathology identified the isolated organisms as Aspergillus species (n = 3) and Fusarium species (n = 2) in the corneal buttons. Conclusion: The differences in VA between the three methods were not statistically significant, indicating no treatment method superior to others (inter-group). However, in Group I, there was a significant difference in VA between the final postoperative follow-up period and baseline (p = 0.0019). There was no difference in VA between these time intervals in either Group II (p = 0.0671) or Group III (p = 0.1505). Within-group or intra-group analysis reveals that the Group I method is more effective for VA. The success rate of the method depended cumulatively on the duration of intracameral voriconazole in the anterior chamber, non-drainage of hypopyon, and individual clinical response.

Treatment Outcome of Wet Age-Related Macular Degeneration Management in Thailand: A Retrospective Real-World Study (TOWER Study).

IntroductionTo present real-world outcomes of neovascular age-related macular degeneration (nAMD) management in Thailand.MethodsThis multicenter retrospective study reviewed medical records of naive nAMD patients diagnosed from 1 January 2016 until 31 December 2018. The patients received at least one intravitreal anti-vascular endothelial growth factor (VEGF) treatment and had captured visual acuity (VA) at baseline and at month 12. Treatment outcomes were assessed at month 12, 24, and 36. The primary outcome was a mean change in VA from baseline to month 12.ResultsFive hundred seventy-two (572) eyes were included in this study and of these eyes, 222 and 96 had 2- and 3-year follow-up periods, respectively. At month 12, the mean improvement of VA (ETDRS letter) was six letters (P < 0.0001), and central retinal thickness (CRT) decreased on average by 104 microns (P < 0.0001). However, visual improvement by 0.1 letters at month 36 did not show statistical significance. The presence of fluid was found in approximately half of patients throughout the study period (45.98%, 48.85%, and 50.91% at month 12, 24, and 36, respectively). Mean number of injections (SD) was 6.06 (3.00), 3.44 (2.94), and 2.71 (3.07) for years 1, 2, and 3, respectively. The mean number of visits (SD) in year 1 was 9.01 (2.60) and declined to 5.67 (2.69) in year 2 and 4.93 (2.49) in year 3. Patients who had an average injection interval of ≤ 8 weeks were 74.46% in year 1, 51.28% in year 2, and 45.24 in year 3; 35.31% of patients were lost to follow-up.ConclusionsThis analysis reflects real-world nAMD management with significant improvement of outcomes. At the same time, the study reveals unmet needs in anti-VEGF therapy in nAMD including persistent disease activities, inadequacy of available treatment, and lack of treatment adherence leading to visual deterioration in the long-term.

Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration.

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Vitrectomy versus Combined Vitrectomy and Scleral Buckle for Repair of Primary Rhegmatogenous Retinal Detachment with Vitreous Hemorrhage

To compare pars plana vitrectomy (PPV) with combined PPV and scleral buckle (PPV/SB) for repair of primary rhegmatogenous retinal detachment (RRD) with associated vitreous hemorrhage (VH). Retrospective, observational study. Patients with RRD and associated VH who underwent PPV or PPV/SB from January 1, 2010, through August 31, 2020, were analyzed. We performed a single-institution, retrospective, observational study of 224 eyes with RRD and VH at the time of detachment. We excluded eyes with <6 months of follow-up, a prior history of retinal detachment (RD) repair with vitrectomy or SB, VH that resolved before surgical intervention, and tractional or combined tractional and rhegmatogenous detachments. Single-surgery anatomic success (SSAS) at 6 months, defined as no recurrent RD requiring surgical intervention. Pars plana vitrectomy and PPV/SB were performed on 138 eyes (62%) and 85 eyes (38%), respectively. The mean age of the PPV and PPV/SB patients was 61.9 and 60.2 years, respectively. Single-surgery anatomic success was achieved in 107 of 138 eyes (77.5%) that underwent PPV and 78 of 85 eyes (91.7%) that underwent PPV/SB. The difference in SSAS between types of treatment was significant (P= 0.006). Mean visual acuity improvement in the PPV/SB group was 0.54 logMAR units greater than that in the PPV group (P= 0.126). The incidence of postoperative proliferative vitreoretinopathy in the PPV/SB group (11.7%) was lower than that in the PPV group (19.5%; P= 0.128). The rate of repeat PPV for non-RD reasons was similar for both the groups (P= 0.437). Final reattachment status was achieved in 137 of the 138 and 84 of the 85 eyes in the PPV and PPV/SB groups, respectively. Final visual acuity improvement was significantly better in eyes with PPV/SB than in eyes with PPV alone (logMAR 2.12 vs. 1.26, respectively; P= 0.011). In patients with RRD and VH, SSAS was superior in patients treated with PPV/SB compared with those treated with PPV alone. Although not significantly different, the PPV/SB group had better visual outcomes and a lower postoperative proliferative vitreoretinopathy rate.

Safety of Intravitreal Gene Therapy for Treatment of Subjects with Leber Hereditary Optic Neuropathy due to Mutations in the Mitochondrial ND4 Gene: The REVEAL Study.

BackgroundLeber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease whose primary clinical manifestation is bilateral visual loss. Only a single therapy, idebenone, is approved in Europe for use in exceptional circumstances and no therapy is currently approved in the USA. LHON remains a disease with a high unmet medical need.ObjectiveThis is a report of an open-label, single-center, dose-escalation study that evaluated the safety and tolerability of lenadogene nolparvovec in 15 subjects with LHON for up to 5 years following a single intravitreal injection at four dose levels.MethodsSubjects were enrolled sequentially in four cohorts followed by an additional cohort at the dose selected, and safety was assessed by an independent data safety monitoring board (DSMB) prior to any dose escalation.ResultsOverall, the treatment was well tolerated during the 5-year follow-up. No serious adverse events were considered related to treatment, no unexpected adverse events occurred, and no grade 3 or 4 Common Terminology Criteria for Adverse Events were reported. Anterior chamber inflammation and vitritis were mostly managed with topical steroids, and ocular inflammation was considered to be dose limiting by the DSMB based on the benefits/risks for the subjects. Analysis of the logarithm of the minimal angle of resolution (LogMAR) visual acuity in both treated and untreated eyes showed clinically relevant and durable improvements compared with baseline. Mean improvements of − 0.44 and − 0.49 LogMAR for treated and untreated eyes, respectively, were noted, with a mean (± standard deviation) final value of LogMAR + 1.96 ± 0.60 and + 1.65 ± 0.34, respectively, at 5 years post-treatment administration. For the six subjects treated with the optimal dose level (9 × 1010 viral genomes [vg]/eye), the mean visual acuity improvement from baseline reached − 0.68 LogMAR for treated eyes and − 0.64 LogMAR for untreated eyes, with a mean final value of LogMAR + 1.77 ± 0.52 and + 1.78 ± 0.34, respectively. While there was a meaningful improvement in visual acuity for REVEAL subjects, the final visual acuity was less favorable than that seen in the two subsequent pivotal phase III studies in which subjects were treated earlier during the course of their disease.ConclusionLenadogene nolparvovec was well tolerated with a good safety profile during 5 years of follow-up and may offer meaningful lasting improvements in vision for this LHON population.Clinical Trial NumberEUDRACT N° 2013-001405-90.

The Influence of Crescent-Shaped Selective Internal Limiting Membrane Staining on Vital Dye Toxicity in Temporal Inverted Flap Technique

ABSTRACT Purpose: To investigate the macular function and morphology after temporal inverted internal limiting membrane (ILM) flap technique with and without staining of the ILM flap in contact with the retinal pigment epithelium (RPE). Materials and Methods: This retrospective study included 30 patients with idiopathic macular hole (MH), who underwent 27 G vitrectomy and temporal inverted ILM flap technique with brillant blue G (BBG) assisted ILM staining. In Group 1 (n = 16), a large bubble of perfluorocarbon liquid (PFCL) measuring approximately 6-disc diameters was used to cover the hole and central part of the ILM flap whereas in Group 2 (n = 14), only a small drop of PFCL to merely cover the MH was used. Complete ophthalmic examination including microperimetry (MP), optical coherence tomography (OCT) was performed preoperatively, 6 months after surgery. Results: MH closure was achieved in all the eyes in both groups. The sizes of ellipsoid zone (EZ) and external limiting membrane (ELM) defect significantly decreased after surgery relative to the baseline width in both groups (p < .05 for all). The mean improvement in visual acuity (p = .896) and retinal sensitivity was similiar between groups (p = .409). Accordingly, the postoperative mean lengths of the EZ (p = .254) and ELM disruption (p = .406) on OCT scans were similiar between groups. However, 3 of the eyes in Group 2 developed cystoid macular edema between postoperative month-1 and month-6. Conclusion: The crescent-shaped selective staining of the ILM flap could prevent prolonged retinal toxicity of vital dyes in inverted ILM flap technique. Further studies involving larger number of patients with longer follow up are needed to determine the impact of this technique in the management of vital dye toxicity.

Intraoperative Complications and Visual Outcomes of Cataract Surgery in Diabetes Mellitus: A Multicenter Database Study

To compare the visual outcome and the rate of intraoperative complications in eyes of diabetic and nondiabetic patients undergoing phacoemulsification over 15 years. Retrospective clinical cohort study. Data of 179,159 eyes that underwent phacoemulsification at 8 centers were classified based on the presence or absence of diabetes mellitus. Visual acuity (VA) was defined as the best value of uncorrected or corrected distance measure available. For the VA analysis, eyes with co-pathologies or combined surgical procedures were further excluded, leaving a subset of 90,729 eyes. Main outcome measures were logarithm of the minimum angle of resolution (logMAR) VA at 4-12weeks postoperatively, and rate of intraoperative complications. Cataract surgery in eyes of diabetic patients was associated with an improvement in mean VA of 0.48 logMAR (5 Snellen lines). Mean postoperative VA was slightly worse in diabetic compared to nondiabetic group (logMAR 0.23 vs 0.13; Snellen 20/30 vs 20/25; P < .0001) and the proportions of eyes achieving a visual gain of ≥3 Snellen lines (≥0.3 logMAR) was lower in the diabetic group (56.6% vs 63.5%; P < .0001). There was a linear relationship between diabetic retinopathy severity and worse postoperative visual acuity (β coefficient 0.098 to 0.288; P < .0001). We observed higher rates of posterior capsule rupture (2.3% vs 1.6%; P < .001) and dropped nuclear fragments (0.3% vs 0.2%; P < .001) in the diabetic group. Postoperative VA negatively correlated with diabetes and diabetic retinopathy severity. Eyes of diabetic subjects had higher risks of posterior capsule rupture.

Intravitreal Sepofarsen for Leber Congenital Amaurosis Type 10 (LCA10)

Background: Sepofarsen is an RNA antisense oligonucleotide (AON) targeting the common c.2991+1655A>G mutation in the CEP290 gene to treat Leber congenital amaurosis type 10 (LCA10), a condition with severe childhood-onset vision loss or blindness. Methods: In this 12-month, multicenter, open-label, multiple-dose, dose-escalation, phase 1b/2 trial, patients with LCA10 received up to four doses of intravitreal sepofarsen in the worse-seeing eye. Primary end point was safety; secondary end points included vision outcome measures. Findings: Of 11 patients enrolled (8–44 years of age), six received loading/maintenance doses of sepofarsen of 160 µg/80 µg and five received 320 µg/160 µg. Reported cases of cataracts, mild cystoid macular edema, and retinal thinning were 3, 0, and 0, respectively, in the 160-µg/80-µg group and 5, 2, and 2 in the 320-µg/160-µg group. Pooled data (n=11) showed improvements from baseline to Month 12 in treated eyes vs untreated eyes in mean ± standard error of the mean best-corrected visual acuity (BCVA: −0·55 ± 0·26 vs −0·12 ± 0·07 logarithm of the minimum angle of resolution [logMAR], p<0·05), red full-field stimulus test (FST: − 0·91 ± 0·18 vs −0·16 ± 0·16 logarithm of candela per square meter [log cd/m2], p<0·01), and blue FST (−0·79 ± 0·23 vs +0·02 ± 0·11 log cd/m2, p<0·02). The 160-µg/80-µg group (n=6) showed improvement in BCVA (−0·93 ± 0·43 vs −0·22 ± 0·11 logMAR, p=0·13), red FST (−0·66 ± 0·14 vs +0·05 ± 0·17 log cd/m2, p<0·05), and blue FST (−0·63 ± 0·31 vs +0·12 ± 0·16 log cd/m2, p=0·09). Interpretation: Sepofarsen had a manageable safety profile in patients with LCA10. Statistically significant differences were observed for the within-subject improvement in mean visual acuity and FST. These therapeutic benefits add to the accumulating evidence for the clinical utility of targeted AONs in genetic disorders. A phase 2/3 pivotal trial is underway. Trial Registration: NCT03140969. Funding Statement: This trial (NCT03140969) was sponsored and funded by ProQR Therapeutics, Leiden, The Netherlands. Declaration of Interests: SRR, AVC report grant funding from ProQR during the conduct of the study. AVD reports grants and other from ProQr, during the conduct of the study; personal fees from Medscape and Novartis, grants from Spark and NIH, patent Novartis with royalties paid to Spark and a patent University of Iowa issued to Spark, outside the submitted work. BPL reports grants and non-financial support from ProQR Therapeutics, grants from Fund for Research Flanders, during the conduct of the study; grants from GenSight Therapeutics, IVERIC Bio, and Vedere Bio; grants and non-financial support from Novartis Pharma, Spark Therapeutics and RegenXBio, outside the submitted work. CVC reports grants and nonfinancial support from ProQR Therapeutics, during the conduct of the study; grants from GenSight Therapeutics, outside the submitted work. ACH reports grants from ProQR both during the conduct of the study and outside the submitted work. EJ reports grants and non-financial support from ProQR Therapeutics, during the conduct of the study; grants from GenSight Therapeutics, outside the submitted work. JDZ reports grants from ProQR Therapeutics, during the conduct of the study; grants from GenSight Therapeutics, outside the submitted work. RWJC reports other from ProQR Therapeutics, outside the submitted work; a patent (antisense oligonucleotides) for the treatment of Leber congenital amaurosis licensed to ProQR Therapeutics. PA reports share holdings in ProQR. MEC reports grants and personal fees from ProQR, during the conduct of the study; grants and personal fees from Editas Medicine, BridgeBio, and Alia Therapeutics, outside the submitted work. MRS, WDH, FA, GP, and AG are employees of ProQR. DR is a strategic advisor of ProQR. SGJ, AVD, IH, MM, WP, EHS, JW, AVG, AKK, CAP, AS, AJR, EV, FN, and CH have nothing to disclose. Ethics Approval Statement: The protocol and informed consent form were approved by the institutional review board or independent ethics committee at each investigational site before trial initiation. The trial was conducted in accordance with the ethical principles of Good Clinical Practice and the Declaration of Helsinki. Adult participants provided written informed consent. Age-appropriate assent and permission from the parent or legal guardian were obtained for children.

Silicone oil tamponade for persistent macular holes.

A variety of treatment strategies have been proposed for macular holes that persist or recur after surgery, and the debate about the best re-treatment approach is ongoing. To allow for a comparison with alternative surgical therapies, we assessed the anatomical and functional outcome of atemporary tamponade with conventional silicone oil in persistent or recurrent full-thickness macular holes. We retrospectively investigated consecutive patients with full-thickness macular holes that persisted or recurred following vitrectomy with internal limiting membrane peeling and gas tamponade. All patients received re-treatment by temporary tamponade of silicone oil and were allowed free postoperative positioning. Anatomical closure rate was assessed by optical coherence tomography, and change of best-corrected visual acuity (BCVA) was analyzed. A total of 33 eyes of 33 consecutive patients were included. Macular hole closure following silicone oil tamponade was achieved in 30 of 33 eyes (90.9%). Median BCVA improved from 1.00 logMAR (interquartile range, 0.60-1.00) to 0.65 logMAR (0.49-1.00; p = 0.010) after silicone oil removal. In patients with macular hole closure, 61.3% exhibited functional improvement with median BCVA changing from 1.00 logMAR (0.70-1.00) to 0.60 logMAR (0.49-1.00; p = 0.0005). Mean minimal linear diameter of macular holes before primary surgery was 391.0 µm (±137.8; range 133-630), and 48.5% of macular holes were >400 µm in diameter. Treatment of persistent or recurrent full-thickness macular holes by temporary conventional silicone oil tamponade without postoperative positioning results in a high closure rate and a significant mean improvement of visual acuity.