Visual Acuity Gain Research Articles

Surgical Treatment for Diabetic Macular Edema

Diabetic macular edema (DME) is defined as excess fluid accumulation within the retina in the macular area, and when it is centered on the fovea it is the most common cause of decreased visual acuity in patients with diabetic retinopathy. The development of diabetic macular edema is closely related to the duration of diabetes, poor glycemic control, and type 2 diabetes on insulin therapy. The first-line therapy in diabetic macular edema has been the intravitreal injection of anti-vascular endothelial growth factors (VEGF). Other treatment modalities are intravitreal corticosteroid injection and focal laser photocoagulation. However, the efficacy of intravitreal therapy may decrease significantly over time, especially in the presence of vitreomacular traction, tight posterior hyaloid, or epiretinal membrane (ERM). At this stage, pars plana vitrectomy (PPV) is preferred as an alternative treatment method in eyes with chronic DME resistant to intravitreal injections. The vitreous of diabetic patients contains high amounts of VEGF and Angiotensin 2, which cause DME, and cytokines such as interleukin-6 and ICAM-1. In addition, due to the enzymes, it contains, the vitreous causes cross-linking and thickening of the collagen fibers in its structure, causing tight adhesion and traction on the macula. The mechanism of action of pars plana vitrectomy in macular edema can be explained by removing the vitreous and vitreomacular tractions. Vitrectomy may also increase retinal oxygenation. Selection of the appropriate case is important. The undisturbed integrity of the outer retinal layers including the external limiting membrane(ELM) and the ellipsoid zone, no preoperative foveal ischemia, and performing surgery early before ELM is damaged, have been found to be related to better postoperative visual acuity gain. Further, prospective, randomized, controlled studies with large series including detailed parameters and long follow-up evaluating the efficacy of surgical treatment in diabetic macular edema are warranted.

Impact of patient adherence on the efficacy of penetrating keratoplasty

Objective: to determine the relationship between adherence to treatment in patients undergoing penetrating keratoplasty (PKP) and corneal graft survival over a 12-month follow-up period. Material and methods. A retrospective analysis of 56 patients who underwent "high risk" PKP was performed. Patients were divided into 2 groups according to their compliance. The full compliance group included those with more than 90% of visits within the first year after the intervention; the poor compliance group included those with more than 10% of missed visits. Results. The high adherence group was characterised by a higher proportion of women (p=0.033), a mean 7 years younger age of the patients (p=0.021) and a predominance of higher education (p=0.014). One year after PKP, patients with complete compliance (74%) were more likely to have a favourable outcome than those with incomplete compliance (48%) (p=0.046). The calculation of the odds ratio (OR 3.52; Cl: 1.1362-10.88; p=0.045) indicated a statistically significant role of treatment adherence as a factor in keratoplasty efficacy. The high compliance group had a visual acuity gain of 2 lines at 12 months (p=0.003). Conclusion. Compliance after corneal transplantation has a significant impact on graft survival and clinical outcome. The development and implementation of a set of measures to increase adherence could significantly improve the safety and efficacy of this high-tech treatment for patients with disabling corneal pathology.

Two different initial treatment regimens of Conbercept in diabetic macular edema: 12-month results from a multicenter randomized controlled study

BackgroundThe optimal treatment regimen for diabetic macular edema (DME) and predictors for its treatment`s outcome need emerging evidence but currently poorly studied. MethodsA prospective, multicenter, open label randomized controlled study among adult patients with DME was conducted. Eyes were randomized to three or six doses initial Conbercept treatments. Additional injections were suggested pro re nata (PRN) over 12 months. Optical coherence tomography angiography (OCTA) was adopted to quantify the macular vessel density. Visual acuity gain and anatomical improvement and their associated factors were evaluated by multivariable linear regression. Results41 patients with 59 eyes participated in current study. Patients in both 3 + PRN (n = 32 eyes) or 6 + PRN (n = 27 eyes) treatments experienced similar best-corrected visual acuity (BCVA) gain and anatomical improvement, including the central macular thickness, foveal avascular aone (FAZ) and the retinal vessel density. Over 12 months, eyes in the 6 + PRN group received better changes of the deep capillary plexus (2.53 ± 5.45%). In multivariate linear regression, the age significantly affected visual outcome in 3 + PRN group (β = -0.014, P = 0.028), while the initial CMT (β = -0.001, P = 0.022) and FAZ area (β = -0.946, P = 0.007) associated with visual outcome in 6 + PRN group. Furthermore, the duration of diabetes exhibited significant results on CMT among 3 + PRN group (β= -7.516, P = 0.04). ConclusionsBoth 3 + and 6 + initial treatment regimens of Conbercept loading dose achieved parallel anatomical and functional visual improvement, while 6 + group had a trend of better treatment outcome. Older age, higher initial CMT and longer duration of diabetes might influence the clinical outcomes over 12 months from baseline.

Paediatric cataract surgery with 27G vitrectomy instrumentation: the Ghent University Hospital Experience.

To describe a cohort of paediatric patients who underwent unilateral or bilateral lens extractions at Ghent University hospital using the Dutch Ophthalmic Research Center (D.O.R.C.) ultra-short 27G vitrectomy system. Retrospective analysis of the medical and surgical records of all children that underwent lens extraction between September 2016 and September 2020 using the D.O.R.C. ultra-short 27G vitrectomy system. Seventy-two eyes of 52 patients were included. The most important aetiologies in this study were of secondary (25.5%), developmental (13.7%), or genetic (13.7%) nature. No definitive cause could be established in more than a quarter of cases (27.5%) despite extensive work-up, them being deemed idiopathic. The remainder of cases (19.6%) was not assigned a final aetiologic designation at the time of the study due to contradicting or missing diagnostic data. This study could not identify any cataract cases related to infection or trauma. Surgical complications rate was 61.1% of which posterior capsule opacification was the most frequent with a rate of 25%. A significant short-term postoperative best-corrected visual acuity gain (≤ -0.2 LogMAR) was observed in 60.5% of eyes for which usable acuity data were available (n = 38). Many different instruments and techniques have been described and used in the context of paediatric lens extractions, each with its advantages and disadvantages. This study illustrates that an ultra-short 27G vitrectomy system can be used to perform paediatric lens extractions with good surgical outcomes. Further studies and comparative trials are needed to ascertain this further.

Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study

AimTo evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF)...

Magnitude of Visual Acuity Change with ETDRS versus Snellen Testing in Clinical Trials: Implications for Clinic-Based Outcomes

To compare visual acuity (VA) changes using standardized ETDRS best-corrected visual acuity (BCVA) and nonstandardized Snellen VA among subjects enrolled in clinical trials. Retrospective study. Patients enrolled in prospective clinical trials at 3 urban retina practices. Best available Snellen VA at the clinic visit before study entry and after exit were compared with the ETDRS BCVA at trial entry and exit. The correlation and discrepancies between Snellen VA and ETDRS methods as well as the VA changes from trial entry to exit were evaluated. The discrepancy between VA change from trial entry to exit using Snellen VA versus ETDRS BCVA methods. A total of 273 eyes were included. The mean (standard deviation [SD]) Snellen VA was 58.1 (20) ETDRS-equivalent letters (Snellen 20/69) at the clinic visit before trial entry and 61.6 (21) ETDRS-equivalent letters (Snellen 20/59) at the visit after trial exit. The mean (SD) ETDRS BCVA was 65.5 (16) letters (Snellen 20/49) at trial entry and 70.5 (17) letters (Snellen 20/39) at trial exit. The mean VA change from trial entry to exit was not significantly different for ETDRS (5 letters of vision gain) compared with Snellen (3.6 letters of vision gain) methods (P= 0.061). Eyes with baseline Snellen VA 20/50 or worse gained significantly more letters using Snellen (9.3±22.3 letters) compared with ETDRS (5.2 ± 18.7 letters; P= 0.012). Among eyes with baseline Snellen VA of > 20/50, VA gain was significantly greater with the ETDRS method (4.9 ± 12.3 letters) compared with Snellen (-1.5 ± 12.3 letters; P < 0.001). The mean VA change from clinical trial entry to exit was similar between the ETDRS and Snellen methods. However, among patients with worse baseline Snellen vision, the magnitude of VA change was greater with Snellen compared with ETDRS, whereas among those with better baseline vision, this magnitude was greater with the ETDRS method. Understanding the proportion of the study population with varying VA levels may have implications for interpreting VA outcomes from retrospective clinic-based studies compared with those reported in clinical trials. Proprietary or commercial disclosure may be found after the references.

Cataract Surgery in Patients With Uveitis Treated With Systemic Therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study: Risk Factors and Outcomes

To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression. Cohort study of participants from a randomized clinical trial. A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery. The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio [HR] 2.86, 95% CI 1.52, 5.42; P=.001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P=.005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P=.004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P=.07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data. Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.

0.18 MG FLUOCINOLONE ACETONIDE INSERT FOR THE TREATMENT OF CHRONIC POSTOPERATIVE PSEUDOPHAKIC CYSTOID MACULAR EDEMA.

To report the outcomes of the 0.18 mg fluocinolone acetonide insert (FAi) in the treatment of chronic (>6 months) postoperative cystoid macular edema after cataract surgery. This was a retrospective consecutive case series of eyes with chronic postoperative cystoid macular edema treated with the FAi. Visual acuity, intraocular pressure, optical coherence tomography metrics, and supplemental therapies were extracted from the charts before and at 3, 6, 12, 18, and 21 months after FAi placement, when available. Nineteen eyes of 13 patients with chronic postoperative cystoid macular edema after cataract surgery underwent FAi placement with an average follow-up of 15.4 months. Ten eyes (52.6%) had a ≥2-line gain in visual acuity. Sixteen eyes (84.2%) had a ≥20% reduction in optical coherence tomography central subfield thickness. Eight eyes (42.1%) had complete resolution of CME. Improvements in central subfield thickness and visual acuity were sustained throughout individual follow-up. Compared with 18 eyes (94.7%) requiring local corticosteroid supplementation before FAi, only six eyes (31.6%) required supplementation after FAi. Similarly, of the 12 eyes (63.2%) that were on corticosteroid drops before FAi, only 3 (15.8%) required drops after FAi. Eyes with chronic postoperative cystoid macular edema after cataract surgery treated with the FAi had improved and sustained visual acuity and optical coherence tomography metrics, along with a reduction in supplemental treatment burden.

Anti-vascular endothelial growth factor dosing frequency and visual outcomes in macular oedema following branch retinal vein occlusion

ObjectivesTo determine the relationship between treatment frequency with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes in eyes with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) in US clinical practice.MethodsStudy eyes that initiated anti-VEGF injections between January 2012 and May 2016 were followed for ≥1 year in a retrospective analysis of medical records (Vestrum Health database). Eyes were analysed in 2 cohorts by treatment duration (years 1 and 2) and then in 2 subcohorts by injection frequency (≤6 or ≥7 injections/year).ResultsAmong 3099 eyes with MO secondary to BRVO, 1197 (38.6%) received ≤6 injections (mean injections, 4.6; baseline mean VA, 53 letters) and 1902 (61.4%) received ≥7 injections through 1 year (mean injections, 8.8; baseline mean VA, 52 letters). At year 1, mean VA gain from baseline was 10.4 versus 13.9 letters in eyes receiving ≤6 versus ≥7 injections (p < 0.001). At year 2, mean VA in eyes receiving ≤6 (n = 42) versus ≥7 injections (n = 227) was 64 versus 68 letters, respectively (p = 0.19). Mean VA change between the start and end of year 2 in eyes receiving ≥7 injections in year 1 and ≤6 in year 2 differed significantly from that of eyes receiving ≥7 injections in both years (–3.0 vs 0.7 letters, respectively; p < 0.001).ConclusionsIn routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with MO secondary to BRVO.

The MATE trial: a multicentre, mixed-methodology, pilot, randomised controlled trial in neovascular age-related macular degeneration

Background/objectivesIn healthcare research investigating complex interventions, gaps in understanding of processes can be filled by using qualitative methods alongside a quantitative approach. The aim of this mixed-methods pilot trial was to provide feasibility evidence comparing two treatment regimens for neovascular age-related macular degeneration (nAMD) to inform a future large-scale randomised controlled trial (RCT).Subjects/methodsForty-four treatment-naïve nAMD patients were followed over 24 months and randomised to one of two treatment regimens: standard care (SC) or treat and extend (T&E). The primary objective evaluated feasibility of the MATE trial via evaluations of screening logs for recruitment rates, nonparticipation and screen fails, whilst qualitative in-depth interviews with key study staff evaluated the recruitment phase and running of the trial. The secondary objective assessed changes in visual acuity and central retinal thickness (CRT) between the two treatment arms.ResultsThe overall recruitment rate was 3.07 participants per month with a 40.8% non-participation rate, 18.51% screen-failure rate and 15% withdrawal/non-completion rate. Key themes in the recruitment phase included human factors, protocol-related issues, recruitment processes and challenges. Both treatment regimens showed a trend towards a visual acuity gain at month 12 which was not maintained at month 24, whilst CRT reduced similarly in both regimens over the same time period. These were achieved with one less treatment following a T&E regimen.ConclusionThis mixed-methodology, pilot RCT achieved its pre-defined recruitment, nonparticipation and screen failure rates, thus deeming it a success. With some minor protocol amendments, progression to a large-scale RCT will be achievable.

Prospective, Observational, Multicenter, Real-World Study of the Efficacy, Safety, and Pattern of Use of the Dexamethasone Intravitreal Implant in Diabetic Macular Edema in France: Short-Term Outcomes of LOUVRE 3.

To evaluate real-world efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in diabetic macular edema (DME) in France. In this prospective, multicenter, observational, noncomparative, post-reimbursement study, consecutively enrolled patients with DME had a baseline evaluation on day0. Those treated with DEX on day0 were to be reevaluated at week6 and months6, 12, 18, and 24. DEX retreatment and/or alternative therapies were allowed during follow-up. The primary outcome measure was themaximum best corrected visual acuity (BCVA) gain from baseline during follow-up. Secondary outcome measures included time to maximum BCVA gain, patients (%) with prespecified BCVA gains from baseline at each visit, maximum central retinal thickness (CRT) reduction from baseline, patients (%) with CRT reduction ≥ 20% from baseline at each visit, patients (%) with DME resolution (per investigator judgement), and adverse events (AEs). Of 112 patients/eyes with DME for 3.5years (mean) at baseline, 80 (including 86.1% previously treated) received DEX on day0 and were analyzed for efficacy. Early study termination precluded collection of ≥ 12-month efficacy data. Patients received 1.4 DEX injections over 8.3months (averages). The maximum BCVA gain from baseline was 3.6 letters, reached after 77.2days (averages); 24.6% (week6) and 15.0% (month6) of patients experienced ≥ 10-letter BCVA gains from baseline. The mean maximum CRT reduction from baseline was -146.4µm; 61.4% (week6) and 36.0% (month6) of patients had CRT reductions ≥ 20% from baseline, and 68.1% reported DME resolution at least once during follow-up. Ocular hypertension (n = 8, 12.1%) was the most frequent treatment-related AE. LOUVRE 3 confirmed that DEX improves BCVA andCRT, even in a patient population that had predominantly received DEX before enrollment in the study, and showed that DME resolution was observed during follow-up. DEX tolerability was consistent with published data, supporting treatment benefits in DME. NCT03003416.

The impact of 360-laser barricade on outcomes of vitrectomy for pseudophakic retinal detachment; The Manchester Pseudophakic Retinal Detachment Study.

To investigate the anatomical and functional outcomes and specifically, the effect of 360-degree barrier-laser, in pars plana vitrectomy (PPV) for primary pseudophakic rhegmatogenous retinal detachment (PRD). We conducted a single-centre retrospective, continuous and comparative study on eyes that had undergone PPV with focal-retinopexy (laser or cryotherapy) versus 360-laser for PRD repair between 2011-2020 at a single tertiary vitreoretinal centre in the UK. Primary outcomes were single surgery anatomical success (SSAS) rate and final postoperative visual acuity (VA). Multivariable regression covariates for primary re-detachment included age, gender, onset-of-detachment, pre-operative VA, ocular co-morbidities, macula-status, majority inferior (vs superior) PRD, number-of-tears and PRD extent (in clock-hours), 360-laser barricade, and perfluorocarbon liquid (PFCL) use. For VA gain, primary re-detachment was added as a covariate. We included 467 eyes with a mean follow-up of 388 (161) days. The SSAS was 444/467 (95.1%) overall, and 351/370 (94.9%) and 93/97 (95.9%) in focal-retinopexy and 360-laser groups, respectively (p = 0.798). Compared to the focal-retinopexy group, the 360-laser group had significantly worse post-operative VA but similar logMAR gain (p = 0.812). A multivariable binary logistic regression found that only PFCL use was linked with increased primary re-detachment (OR:5.32 [p = 0.048]) and 360-laser did not contribute to increased SSAS. A multivariable linear regression analysis showed that poor logMAR gain was significantly associated with better pre-operative logMAR, ocular co-morbidities, greater PRD extent, use of 360-laser and primary re-detachment. However, when excluding macula-off RD (n = 211), 360-laser was no longer significant (p = 0.088). Prophylactic 360-laser does not seem to impact on SSAS and functional outcomes following PPV for primary PRD.

Predictive value of pigment epithelial detachment markers for visual acuity outcomes in neovascular age-related macular degeneration

BackgroundTo determine the predictive value of quantitative morphological parameters for pigment epithelial detachment (PED) of neovascular age-related macular degeneration (nAMD) patients.MethodsOne eye from each of 159 patients with nAMD were studied. Polypoidal choroidal vasculopathy (PCV) group included 77 eyes, and non-PCV group 82. Patients received conbercept 0.05 ml (0.5 mg) in a 3 + ProReNata (PRN) treatment regimen. Correlations between retinal morphologic parameters at baseline and best-corrected visual acuity (BCVA) gain at 3 or 12 months after treatment (structure–function correlations) were assessed. Optical coherence tomography (OCT) scans were used to assess retinal morphologic features including intraretinal cystoid fluid (IRC), subretinal fluid (SRF), PED or PED type (PEDT), and vitreomacular adhesion (VMA). Greatest height (PEDH) and width of PED (PEDW), and volume of PED (PEDV) at baseline were also measured.ResultsFor non-PCV group, BCVA gain from 3 or 12 months after treatment was negatively correlated with PEDV at baseline (r = -0.329, -0.312, P = 0.027, 0.037). BCVA gain at 12 months after treatment was negatively correlated with PEDW at baseline (r = -0.305, P = 0.044). For PCV group, there were no correlations with PEDV, PEDH, PEDW, and PEDT in BCVA gain between baseline and 3 or 12 months after treatment (P > 0.05). SRF, IRC, VMA at baseline did not correlate with short-term and long-term BCVA gain in patients with nAMD (P > 0.05).ConclusionFor patients with non-PCV, PEDV at baseline was negatively correlated with short-term and long-term BCVA gain, and PEDW was negatively correlated with long-term BCVA gain. On the contrary, quantitative morphological parameters for PED at baseline had no correlation with BCVA gain in patients with PCV.

Repeat Surgery following Temporal Inverted ILM Flap Technique: Next Step after Primary Failure.

We aimed to report our surgical experience with repeat surgery as the next step after an unsuccessful hole closure with the primary single-layered temporal inverted flap technique (IFT). We identified cases with persistent macular holes by reviewing the records of eyes that underwent IFT between October 2018 and October 2021. These cases were evaluated for hole features, anatomical closure, and visual improvement before and after the first and second surgeries. In addition, the technique applied in repeat surgery was recorded. Optical coherence tomography (OCT) images at follow-up were used to evaluate the flap position. A persistent hole was identified in 11 (6.4%) of 172patients who underwent IFT. An inferotemporal displacement was observed in seven eyes, while no flap could be identified in the OCT images of the other four eyes. In the second surgery, the old flap was reinverted in one eye, and a new flap was created from the superior region in five eyes and the nasal region in the other five eyes and was stabilized under perfluorocarbon liquid. A gas tamponade (C3F8/SF6) was used in all patients at the end of surgery. The minimum hole diameter was > 400 µm in all eyes and 100% closure was achieved after the second surgery. Visual acuity gain of ≥ 3 lines was observed in 9 of the 11 eyes (81.8%). The mean visual acuity increase at the last follow-up was significant (p = 0.008). With single-layer temporal IFT in the primary surgery of macular holes, unsuccessful results may be observed due to the flap displacement in the early period. In our series, IFT was applied again with the use of the old flap or the creation of a new flap in the second surgery of the persistent holes, and successful results were obtained.

Real-World Investigation of Impact of Retinal Fluid in Treatment Naïve Eyes Treated with Anti-VEGF for Neovascular Age-Related Macular Degeneration

ABSTRACT Background Traditionally, visual acuity gain and central retinal thickness have been used to measure outcomes when investigating the efficacy of vascular endothelial growth factor (VEGF) inhibitors for patients with neovascular age-related macular degeneration (nARMD). However, localization of retinal fluid may offer additional prognostic value for treatment. The primary aim of this retrospective clinical audit was to investigate whether the presence and location of subretinal fluid has an effect on the visual outcomes of treatment naïve patients with nARMD treated in the real-world setting with VEGF inhibitors. Secondary aims included investigation of change to visual and anatomical outcomes and investigation of the dosing schedule. Methods Retrospective observational study of patients attending one suburban and one regional ophthalmology clinic requiring treatment with VEGF inhibitors for nARMD using single-user non-identifiable data from the Fight Retinal Blindness! Registry from 2014 to 2020. Visual acuity (VA) and central subfield thickness (CST) were recorded at baseline, 3, 6, 12 and 24 months. Results Forty-nine eyes of 42 treatment naïve patients were included for analysis (aged 62–89 years). Almost half (49%) presented with a combination of intra- and subretinal fluid at baseline. Intraretinal fluid was present in 75% of eyes but decreased to 22.7% of eyes by 24 months. VA at baseline was 55 letters, and this improved by 6 letters. The change in VA from baseline to 3, 6 and 12 months was statistically significant (p < .05). The mean change in CST from baseline to 3 months was significant (−76 µm). This change was also observed at the other milestones (p < .001). Conclusions The findings of this study suggest that allowing some subretinal fluid to remain will not affect treatment outcomes.

Treatment of neovascular age-related macular degeneration within 48 h from diagnosis improves long-term functional outcome

PurposeTo evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on the time delay from confirmed diagnosis to treatment initiation. Materials and methodsSeventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared. ResultsLong-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups. ConclusionsAn early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.

A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration

Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab. Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial. Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States. Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab. The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT. Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (± standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 ± 11.61 vs.+10.8 ± 11.52 letters; P= 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 ± 11.32 letters; P= 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm. Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082). Proprietary or commercial disclosure may be found after the references.

Optic nerve head perfusion changes in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab or photocoagulation: a randomized controlled trial.

Proliferative diabetic retinopathy (PDR) is a serious sight-threatening disease, and half of the patients with high-risk PDR can develop legal blindness within 5 years, if left untreated. This study was aimed at comparing panretinal photocoagulation (PRP) and intravitreal ranibizumab injections in terms of radial peripapillary capillary (RPC) density on optical coherence tomography angiography (OCTA) in patients with treatment-naive PDR. This open-label, prospective, randomized clinical trial included 50 patients with treatment-naive PDR with optic disc neovascularization and randomized them into two groups: group 1, with patients undergoing two sessions of PRP 2 weeks apart, and group 2, with patients received three intravitreal ranibizumab injections (0.5 mg) 1 month apart for 3 consecutive months. Patients underwent a full ophthalmological examination, including best-corrected distance visual acuity (BCDVA) measurement in the logarithm of minimal angle of resolution (logMAR) notation and OCTA before intervention and monthly after the last laser session or the first intravitreal ranibizumab injection for 3 months of follow-up. Visual field (VF) was tested at the beginning and end of 3 months. Forty-two (84%) eyes completed the 3-month follow-up, including 22 eyes in the PRP group (88%) and 20 (80%) eyes in the ranibizumab group. The two groups were comparable in terms of demographic characteristics, diabetes duration, baseline BCDVA, glycated hemoglobin level, OCTA parameters, VF indices, and intraocular pressure (all P > 0.05). The RPC density change from baseline to the 3-month follow-up was significantly lower in the PRP group than in the ranibizumab group (mean difference in RPC density change: - 3.61%; 95% confidence interval: - 5.57% to - 1.60%; P = 0.001). The median (interquartile range) logMAR change from baseline to the 3-month follow-up (0.0 [0.2]) was significantly higher in the PRP group than in the ranibizumab group (- 0.15 [0.3]; P < 0.05). The median changes in central foveal thickness from baseline to the 3-month follow-up differed significantly between the two groups (P = 0.001). In eyes with PDR and neovascularization of the disc RPC density on OCTA increased in the ranibizumab group and decreased in the PRP group. Visual acuity gain was higher in the ranibizumab group than in the PRP group. Future multicenter trials addressing our limitations are required to verify the findings of this study.

The Effects of Treatment Regimen on the Initial Management of Macular Neovascularization Subtypes in Age-Related Macular Degeneration

Introduction: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype. Methods: Consecutive treatment-naïve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes. Results: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045). Conclusion: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database

AimTo explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration...