Long term follow up of patients with MNV3 treated with intra-vitreal Aflibercept.

PURPOSE: MNV3 or Retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (nAMD). We present the 5 year long term visual and anatomical outcomes of patients with MNV3 lesions treated with intravitreal Aflibercept. METHODS: This is a prospective study of treatment naïve patients with reading centre graded MNV3 lesions. After the loading phase, the patients received intravitreal Aflibercept as per the View study up to year 3, thereafter it was given on a prn basis. At each visit, best corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) was measured. RESULTS: Thirty one patients reached study completion. Mean BCVA of treated eyes had decreased by 0.6 ETDRS letters at the end of year 5 compared with baseline. At study completion, 81% of eyes had stable vision while 19% of eyes had gained 15 letters or more. At study end, 26% of eyes had BCVA of 6/12 or better, while 19% had lost 15 letters or more (all had central foveal photoreceptor loss). There was a maximal mean reduction in CMT of 164 microns (p = <0.0001) while 68% of maculae were fluid free at study completion. Eighty seven percent of treated eyes developed nascent GA, of which in 74% of eyes was involving the fovea. DISCUSSION: Despite initial improvement in mean BCVA, the improvement in BCVA was not maintained despite good overall control of the MNV3 lesions. The loss of BCVA was most likely due to the majority of eyes developing centre involving macular atrophy.

RETINAL OPTICAL COHERENCE TOMOGRAPHY IMAGING BIOMARKERS: A Review of the Literature.

PURPOSE: The aim of this literature review was to summarize novel optical coherence tomography (OCT) imaging biomarkers that have recently been described in the literature and are frequently encountered clinically. METHODS: The literature was reviewed to identify novel OCT biomarkers reported to date. A descriptive summary of all terms and representative illustrations were provided to highlight the most relevant features. RESULTS: Thirty-seven OCT terminologies were identified. The vitreomacular interface disorder group included the four stages of epiretinal membrane, macular pseudohole, tractional lamellar hole (LH), degenerative LH, cotton ball sign, and foveal crack sign. The age-related macular degeneration group included outer retinal tubulation, multilayered pigment epithelial detachment, prechoroidal cleft, onion sign, double-layer sign, complete outer retinal atrophy, complete retinal pigment epithelium and outer retinal atrophy, and reticular pseudodrusen. The uveitic disorder group consisted of bacillary layer detachment, syphilis placoid, rain-cloud sign, and pitchfork sign. The disorders relating to the toxicity group included flying saucer sign and mitogen-activated protein kinase (MEK) inhibitor-associated retinopathy. The disorders associated with the systemic condition group included choroidal nodules and needle sign. The pachychoroid spectrum group included pachychoroid and brush border pattern. The vascular disorder group included pearl necklace sign, diffuse retinal thickening, disorganization of retinal inner layers, inner nuclear layer microcysts, hyperreflective retinal spots, paracentral acute middle maculopathy, and acute macular neuroretinopathy. The miscellaneous group included omega sign (ω), macular telangiectasia (type 2), and omega sign (Ω). CONCLUSIONS: Thirty-seven OCT terminologies were summarized, and detailed illustrations consolidating the features of each biomarker were included. A nuanced understanding of OCT biomarkers and their clinical significance is essential because of their predictive and prognostic value.

Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab.

PURPOSE: Although previous studies have demonstrated the efficacy of faricimab in treatment-naive patients with neovascular age-related macular degeneration (nAMD), its outcomes in patients switched from aflibercept are less understood. This study aimed to assess clinical anatomical and functional outcomes of switching to faricimab in patients undergoing aflibercept intravitreal injections (IVIs) for nAMD with suboptimal response. DESIGN: Retrospective case series. SUBJECTS: Patients with nAMD at a single tertiary care center who were switched from aflibercept to faricimab due to persistent suboptimal response. METHODS: Patients had received a minimum of 6 consecutive IVIs of aflibercept and showed persistent presence of intraretinal (IRF) or subretinal fluid (SRF) on OCT despite receiving aflibercept at 4 or 6-weekly intervals at the time of the switch. Patients receiving 4-weekly aflibercept were switched with either 2 or 3 loading doses of 4-weekly faricimab injections. Regression models were used to identify predictors of clinical outcomes. MAIN OUTCOME MEASURES: Visual acuity, central macular thickness (CMT), and OCT parameters were assessed preswitch and postswitch. RESULTS: Eighty-one eyes of 68 patients were included. The mean age was 79.1 years (standard deviation: 8.9), and females constituted 53% of cases. A statistically significant reduction in CMT was observed postswitch (P < 0.0001). The proportion of cases with IRF (P = 0.0219) and SRF (P < 0.000) decreased significantly. Overall clinical improvement on OCT was noted in 80% of patients. No significant improvement in ETDRS vision was observed. There was no evidence that switching regimen (2 vs. 3 loading doses) had an independent effect on clinical outcomes. CONCLUSION: Among patients with treatment-resistant nAMD, switching from aflibercept to faricimab may serve as a safe and effective option. Significant anatomical improvements were observed, with a trend toward visual stability. The loading regimen with 2 faricimab injections appeared to be sufficient for nonnaive patients. However, a longer follow-up and larger studies are warranted to confirm these findings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The effect of COVID-19 on referral patterns for clinical electrophysiological testing.

PURPOSE: To provide an overview of the effect that the COVID-19 pandemic has had on visual electrophysiology referral patterns and the subsequent effect this may have on patients. METHODS: All electrodiagnostic tests performed at Kensington Vision and Research Centre, Toronto Canada, in a 3-month period prior to the COVID-19 pandemic (1 September 2019 to 30 November 2019) were compared to a 3-month period after the start of the COVID-19 pandemic (1 September 2021 to 30 November 2021). RESULTS: A total of 502 patients had electrodiagnostic testing carried out in the designated time periods: 292 in the time period prior to the COVID-19 pandemic and 210 patients after. There was a significant change in the reason for referral in patients pre-COVID compared to post-COVID (p = 0.004). There was a 43% reduction in referrals for drug monitoring, 25% reduction for hereditary pathology and a 27% increase in acquired pathology after the start of the COVID-19 pandemic compared to before. CONCLUSIONS: There was a substantial decrease in the total number of patients referred after the start of the COVID-19 pandemic compared to pre-COVID with inherited retinal pathology and drug monitoring patients being 2 populations most affected by the disruption to healthcare services.

Delayed follow-up of medical retina patients due to COVID-19: impact on disease activity and visual acuity.

PURPOSE: The coronavirus pandemic has prompted unprecedented delays to treatment with anti-VEGF intravitreal injections due to the need to reduce hospital attendances and prioritise the patients at highest risk of vision loss. This study aims to quantify the effect of these delays on visual acuity (VA) outcomes and optical coherence tomography (OCT) features for patients receiving treatment for neovascular age-related macular degeneration (nAMD), retinal vein occlusions (RVO) and diabetic macular oedema (DMO) and correlate to the Royal College of Ophthalmologists guidelines (RCOphth). METHODS: A retrospective data analysis of an electronic medical record was performed on a random sample of eyes receiving anti-VEGF injections for nAMD, RVO or DMO. Data collected included age, sex, reason for injection, number of weeks delay if > 8 weeks from that planned, VA at baseline and follow-up and the OCT features, if delayed. For those eyes not delayed, a visual acuity at 20 weeks was recorded to provide a control group. RESULTS: A sample of 981 eyes (858 patients) were analysed. There was a delay in review of 8 weeks or more in 39.6% of patients of which 30.4% had since returned for review (28.4% nAMD, 37.6% RVO and 30.0% DMO). There was no demographic difference identified between the delayed and non-delayed patients; however, the delayed group was significantly more likely to have better vision in their non-treated eye (p = 0.0003). A statistically significant difference was found in the change in VA between the delayed and the not-delayed group for eyes with nAMD (p = 0.001) but not for RVO or DMO. For the delayed group, mean CMT increased by 33 and 100 µm, respectively, for nAMD and RVO and decreased by 7.8 µm for DMO. The VA of 89.7% of DMO eyes returned to baseline, compared to 74.6% and 76.9% of nAMD and RVO eyes. CONCLUSION: The RCOphth guidance to prioritise intravitreal injections for nAMD over DMO appears appropriate in this cohort but not for RVO. Eyes with nAMD experienced the greatest loss of vision with treatment delay, and nAMD and RVO eyes were less likely to return to baseline on restarting treatment.

Desferrioxamine-Related Pseudo-Vitelliform Dystrophy and the Effect of Anti-Vascular Endothelial Growth Factor.

We report a case of a 72-year-old female who developed bilateral pseudo-vitelliform dystrophy after taking desferrioxamine for the treatment of chronic iron overload. The patient then developed a right superior hemiretinal vein occlusion associated with intraretinal fluid in the right eye and was treated with monthly intravitreal aflibercept injections for 3 months followed by as required treatment. In addition to the intraretinal fluid responding to anti-VEGF treatment, there was a reduction in the size of the pseudo-vitelliform subfoveal deposit height, which was not seen in the untreated eye. Our case of an uncommon presentation of desferrioxamine-related maculopathy associated with a vein occlusion and the changes associated with intravitreal anti-VEGF treatment may help with the potential hypotheses of the pathophysiology of desferrioxamine-related pseudo-vitelliform retinal lesions and help with the potential future treatments of the condition.

Acute Macular Neuroretinopathy Associated with Acute Influenza Virus Infection.

Purpose: To describe a prospective case series of patients with acute macular neuroretinopathy (AMN) associated with acute influenza virus infectionMethods: Patients who presented with acute macular neuroretinopathy associated with confirmed influenza virus infection were subject to a detailed clinical history, HLA typing and longitudinal ophthalmological and imaging examinations.Results: Four female patients aged 18 to 32 years were studied. They reported the onset of ocular symptoms between 2 and 5 days after the development of flu like symptoms. Three patients had confirmed acute influenza B infection, while the fourth had influenza A. OCT angiography only demonstrated abnormal choriocapillaris perfusion in 1 patient and early oral Oseltamivir treatment appeared not to affect the ophthalmic outcome in one patient.Conclusion: This is the first report of AMN associated with virologically confirmed acute influenza virus infection. Variation in HLA alleles do not appear to predispose patients to influenza associated AMN.

The Association between Foveal Floor Measurements and Macular Hole Size.

PURPOSE: Determining which factors influence idiopathic macular hole (MH) size is important because it is a major prognostic indicator of treatment success. Foveal pit morphologic features are highly symmetrical within individuals and may influence idiopathic MH size. Using a series of patients with unilateral idiopathic MHs, we examined the foveal floor size of the fellow eye to evaluate its relationship with idiopathic MH size and postoperative outcomes. DESIGN: Retrospective observational study. PARTICIPANTS: Two hundred forty-one participants with a unilateral idiopathic MH treated with surgery and a fellow eye with no ocular pathologic features. METHODS: Both eyes underwent spectral-domain (SD) OCT imaging at the time of surgery. Minimum linear diameter (MLD) and base diameter (BD) defined idiopathic MH size. Foveal floor width (FFW) and minimal foveal thickness defined foveal pit morphologic features of the fellow eye. MAIN OUTCOME MEASURES: Baseline characteristics, SD OCT measurements, and preoperative variables were compared to determine their relationship with idiopathic MH size and postoperative visual acuity (VA) in logarithm of the minimum angle of resolution units. RESULTS: Foveal floor width was correlated with MLD (r = 0.36; P ≤ 0.001) and BD (r = 0.30; P ≤ 0.001), but not postoperative VA. Minimum linear diameter correlated with preoperative VA (r = 0.49; P ≤ 0.0001) and postoperative VA (r = 0.54; P ≤ 0.0001). A 2-stage regression model was developed to predict postoperative VA (r2 = 0.28): preoperative VA (ß = 0.36; P = 0.002) explained 13% of variability and MLD (ß = 0.29; P = 0.002), and idiopathic MH duration (ß = 0.23; P = 0.004) explained a further 16%. CONCLUSIONS: Foveal floor width of the fellow eye in patients with a unilateral idiopathic MH was correlated significantly with idiopathic MH size and may explain some of the variability in idiopathic MH size observed between individuals. However, FFW could not predict postoperative vision.

Incidence, characteristics, outcomes and confidence in managing posterior capsular rupture during cataract surgery in the UK: an ophthalmology trainees' perspective.

PURPOSE: To examine the incidence, characteristics and outcomes of posterior capsular rupture (PCR) cases amongst the ophthalmology trainees and to evaluate the trainees' confidence in managing PCR. METHODS: A two-staged cross-sectional study was carried out between September 2017 and April 2018 in the North East of England, UK. All ophthalmology trainees were surveyed on their confidence level in managing PCR and the characteristics and outcomes of their PCR cases. RESULTS: Fifteen (71.4%) out of 21 trainees completed the study. The mean number of phacoemulsification was 268.9 ± 250.9 cases (range, 0-705) per trainee. There were 82 (1.9%) cases of PCR reported among 4303 phacoemulsification. PCR occurred most commonly during quadrant removal (44.0%) and cortex removal (21.3%). The best-corrected visual acuity (in logMAR) improved significantly from 0.47 ± 0.32 preoperatively to 0.20 ± 0.19 postoperatively (p < 0.001). The supervising consultant took over 80.5% of the PCR cases. The PCR rate decreased significantly from 3.1% at 0-100 cases to 0.6% at 301-400 cases (p = 0.004) and to 0.4% at >500 cases (p = 0.005). Confidence in managing PCR (without supervision) improved from 0% (9/9) at junior level to 50% (3/6) at senior level, and the average number of anterior vitrectomies performed was 0.6 ± 0.9 (range: 0.0-2.0). CONCLUSIONS: We observed a low PCR rate among the trainees in our region, with the majority of cases achieving good visual outcome. A significant reduction in PCR rate was observed at the threshold of >500 cases. There is however a lack of confidence among trainees in managing PCR, highlighting the need for devising new training strategies in this area.

Determinants of vitreomacular traction width: associations with foveal floor width and vitreoretinal interface changes.

To investigate the relationship between vitreomacular traction (VMT) width, foveal floor width (FFW) and other anatomical characteristics between eyes of patients with VMT. Retrospective observational study of unilateral and bilateral VMT cases from two specialist ophthalmic centres in the United Kingdom (UK) between 2016 and 2018. For unilateral VMT cases: VMT width in the affected eye and FFW in the non-affected fellow eye were measured. In bilateral VMT cases: VMT width in both eyes was measured. In all cases, the presence of any associated inner or outer retinal, and vitreoretinal interface (VRI) changes, including epiretinal membrane, was also documented. 88 patients fulfilled the study criteria: 57 having unilateral and 31 bilateral VMT. For unilateral VMT cases, log (VMT) width was significantly correlated with FFW (r = 0.347, p = 0.008). Using stepwise linear regression, FFW (p = 0.004) and VRI changes (p = 0.03) were both significantly associated with VMT width with a R2 of 0.21. In bilateral VMT cases, there was strong positive correlation between log (VMT) width (r = 0.88, p < 0.001), and the presence of any VRI (r = 0.90, p < 0.001) or outer retinal changes (r = 0.50, p < 0.001) between the two eyes. These findings suggest that individual variations in foveal morphology as measured by the FFW, along with the presence of vitreoretinal interface changes, are associated with the extent of VMT width. VMT width, VRI and outer retinal changes were also highly correlated between eyes in bilateral VMT, suggesting that individual patient factors, which may be genetic or acquired, determine their presence and extent.

Photoreceptor Outer Segment on Internal Limiting Membrane after Macular Hole Surgery: Implications for Pathogenesis.

PURPOSE: This report presents a case, which highlights key principles in the pathophysiology of macular holes. It has been hypothesized that anteroposterior (AP) and tangential vitreous traction on the fovea are the primary underlying factors causing macular holes [Nischal and Pearson; in Kanski and Bowling: Clinical Ophthalmology: A Systemic Approach, 2011, pp 629-631]. Spectral domain optical coherence tomography (OCT) has subsequently corroborated this theory in part but shown that AP vitreofoveal traction is the more common scenario [Steel and Lotery: Eye 2013;27:1-21]. METHODS: This study was conducted as a single case report. RESULTS: A 63-year old female presented to her optician with blurred and distorted vision in her left eye. OCT showed a macular hole with a minimum linear diameter of 370 µm, with persistent broad vitreofoveal attachment on both sides of the hole edges. The patient underwent combined left phacoemulsification and pars plana vitrectomy, internal limiting membrane (ILM) peel and gas injection. The ILM was examined by electron microscopy and showed the presence of a cone outer segment on the retinal side. Post-operative OCT at 11 weeks showed a closed hole with recovery of the foveal contour and good vision. CONCLUSION: Our case shows the presence of a photoreceptor outer segment on the retinal side of the ILM and reinforces the importance of tangential traction in the development of some macula holes. The case highlights the theory of transmission of inner retinal forces to the photoreceptors via Müller cells and how a full thickness macular hole defect can occur in the absence of AP vitreomacular traction.

The association between retinal vessel morphology and retinal nerve fiber layer thickness in an elderly population.

BACKGROUND AND OBJECTIVE: To investigate the relationship between retinal vessel morphology (branching coefficient, bifurcation angle, and fractal analysis) and retinal nerve fiber layer (RNFL) thickness in an elderly population. PATIENTS AND METHODS: One hundred and one participants from the Lothian Birth Cohort 1936 (population of people all born in 1936) were studied. RNFL thickness measurements (using optical coherence tomography [OCT]) and digital retinal photographs were collected. The retinal images were analyzed using custom-designed software called the Vascular Assessment and Measurement Platform for Images of the Retina. RESULTS: Greater deviation from the optimal arteriolar branching coefficient was associated with greater RNFL thickness (r = 0.249, P = .028). There was no significant association between RNFL thickness and the other retinal vessel morphology parameters. CONCLUSION: RNFL thickness increased significantly with suboptimality of arteriole branching coefficient. These findings cannot be explained by our current understanding of OCT. OCT-based biomarker metrics require further study to better define retinal neurovascular imaging and anatomy.