Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.

Purpose: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures. Methods: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI. Results: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision. Conclusions: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD. Translational Relevance: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.

Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population.

Purpose: To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents. Methods: This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED. Results: Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae. Conclusions: In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.

Efficacy of a novel personalised aflibercept monotherapy regimen based on polypoidal lesion closure in participants with polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy of aflibercept using a personalised versus fixed regimen in treatment-naïve participants with polypoidal choroidal vasculopathy (PCV). DESIGN: A 52-week, randomised, open-label, non-inferiority, single-centre study that included participants with symptomatic PCV. Participants were randomised (3:1 ratio) to receive either personalised (n=40) or fixed 8-weekly treatment regimen (n=13). The personalised regimen allowed for either early treat and extend (T&E) after week 12 or late T&E with 3 additional 4-weekly aflibercept injections until week 24 in participants with residual polypoidal lesions (PL) on indocyanine green angiography (ICGA) at week 12. MAIN OUTCOMES AND MEASURES: Non-inferiority of personalised to fixed regimen for mean change in best-corrected visual acuity (BCVA) from baseline to week 52 (non-inferiority margin: -5 letters). The key secondary outcomes include reduction in central subfield thickness (CSFT) on optical coherence tomography and the anatomical closure of PL on ICGA. RESULTS: Of the 53 participants, the mean (SD) age was 69.2 (8.1) years, 19 (35.8 %) were male. Personalised group was non-inferior to fixed for the primary end point (+8.1 vs +7.9 letters at week 52, respectively; difference 0.16, 95% CI -2.8 to 2.4, p=0.79). There was greater reduction in mean CSFT (SD) in the personalised versus fixed group (-248.8 (169.9) vs -164.8 (148.9) µm, p=0.03). Closure of PL occurred in 21 (55.2%) and 5 (41.6%) of study eyes in personalised and fixed groups, respectively at week 52 (p=0.41). CONCLUSIONS: Personalised regimen achieved non-inferior BCVA gain and numerically higher PL closure compared with fixed regimen. TRIAL REGISTRATION NUMBER: NCT03117634.

25-years Trends and Risk factors related to Surgical Outcomes of Giant Retinal Tear-Rhegmatogenous Retinal Detachments.

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.

Real-World Treatment Outcomes of Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Asians.

PURPOSE: To describe the 12-month outcomes of treatment-naïve eyes with choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) after initiation of intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy or combination therapy with verteporfin photodynamic therapy (PDT). DESIGN: A 12-month single-center, retrospective, comparative, nonrandomized cohort study. PARTICIPANTS: Patients with AMD or PCV who initiated intravitreal anti-VEGF therapy during 2015. METHODS: Demographics, visual outcomes, OCT, and treatment data were collected at baseline and months 1, 3, 6, and 12 after treatment initiation. Multivariate analysis was performed to identify baseline features predictive of visual maintenance and improvement after 12 months of treatment. MAIN OUTCOME MEASURES: Primary end point was visual acuity (VA) change from baseline to month 12. Secondary end points were treatment exposure and change in central subfield thickness on OCT. RESULTS: A total of 364 patients (165 AMD and 199 PCV) were included. Baseline vision was 41 and 43 logarithm of the minimum angle of resolution (logMAR) letters for AMD and PCV patients, respectively. Patients with AMD and PCV received 5.5 and 5.3 injections (5.0 monotherapy vs. 5.6 combination therapy; mean, 1.2 PDT sessions), respectively. Patients with AMD gained 4.7 logMAR letters after 12 months (P = 0.002), whereas PCV patients gained 6.6 logMAR letters (P = 0.001) and 10.8 logMAR letters (P < 0.001) for monotherapy and combination therapy, respectively. Only patients with presenting VA of fewer than 35 letters (Snellen equivalent, 6/60) achieved significant visual improvement (10.4 letters for AMD, 17.1 letters for PCV with monotherapy, and 35.5 letters for PCV with combination therapy). Predictors of VA gain included number of intravitreal injections (AMD and PCV adjusted odds ratio, 12.1 [P = 0.001] and 12.5 [P = 0.004] for ≥7 injections, respectively) and baseline VA of 20 logMAR letters or fewer (adjusted odds ratio, 3.8 and 10.6 for AMD and PCV, respectively). Age, gender, race, use of PDT or focal laser therapy, and central subfield thickness were not predictive of significant visual gain at 12 months. CONCLUSIONS: In Asian patients, treatment of AMD with anti-VEGF therapy yielded 12-month visual outcomes comparable with those of other real-world studies from Western populations but poorer than those of controlled trials. In contrast, for PCV eyes, anti-VEGF monotherapy and combination therapy with PDT yielded comparable outcomes as those of controlled clinical trials.

Identification of imaging features that determine quality and repeatability of retinal capillary plexus density measurements in OCT angiography.

PURPOSE: Optical coherence tomography angiography (OCT-A) potentially allows for rapid and non-invasive quantification of retinal capillary plexus density in various disease states. This study aims to identify the key features that influenced the repeatability of OCT-A measurements. METHODS: We obtained OCT-A images on two separate visits in 44 healthy eyes from 44 subjects, each imaged with using the Topcon DRI OCT Triton imaging system. The parafoveal vessel density within a 1.5 mm radius centred over the fovea was obtained with the built-in tool for the superficial and deep retinal plexuses. Repeatability of vessel density was determined by intraclass correlation (ICC) and mean variation. We evaluated several image parameters to determine their influence on the repeatability of vessel density measurement in each of the two capillary plexuses. RESULTS: The mean age of the subjects was 70.2±9.2 years, with 64% males. Mean parafoveal vessel density measurements for the first and second visits were 53.3±11.1 and 53.3±10.3 for the superficial plexus and 27.3±8.59 and 27.0±8.78 for the deep plexus. ICC analyses demonstrated that high fine vessel visibility, the absence of motion artefact and software-derived image quality score of 60 or above were necessary to obtain a good (ICC>0.6) or excellent (ICC>0.75) repeatability. CONCLUSIONS: Our study identified the imaging parameters that determined the repeatability of quantitative retinal vessel density measurements. These findings have implications in determining if OCT-A images can be used to accurately evaluate serial changes in retinal vessel density.

Comparison of swept source optical coherence tomography and spectral domain optical coherence tomography in polypoidal choroidal vasculopathy.

BACKGROUND: Swept source optical coherence tomography (SS-OCT, Topcon Medical System, Japan) is known to have longer wavelength than spectral domain OCT (SD-OCT, Spectralis, Heidelberg Engineering, Germany), allowing a deeper penetration into retina and choroidal layers. This objective of this study was to compare the visibility of retinal and choroidal features in polypoidal choroidal vasculopathy (PCV) using SS-OCT and SD-OCT. DESIGN: This study employs prospective comparative observational case series in Singapore National Eye Center. PARTICIPANTS: There were 20 eyes (20 patients) with PCV confirmed with indocyanine green angiogram. METHODS: Six pre-specified OCT parameters (presence of polyps, sharp pigment epithelial detachment [PED] peak, notched PED and visibility of full maximum height of PED, inner segment/outer segment [IS/OS] line and choroid-scleral interface [CSI]) were graded using SS-OCT and SD-OCT. MAIN OUTCOME MEASURES: The Kappa statistics between the two imaging modalities were calculated. RESULTS: Both SS-OCT and SD-OCT were able to detect polypoidal lesions in the majority of eyes (90% and 85%, respectively). However, SS-OCT had better detection for CSI and IS/OS lines (CSI: 80% vs 45%, P = 0.05; IS/OS line: 65% vs 45%, P = 0.34). For sharp PED peak, notched PED, ability to visualize the full PED height and retinal pigment epithelial line, both OCT machines were able to detect in ≥80% of the eyes. CONCLUSION: In conclusion, SS-OCT and SD-OCT appeared to be similarly effective at detecting most features associated with PCV. However, SS-OCT is more superior in detecting the CSI.

Cystoid macular edema in acute presentation of central retinal artery occlusion.

A seventy-six-year-old lady with poor vision of the left eye due to previous retinal detachment presented with acute visual loss of her right eye secondary to central retinal artery occlusion. Clinical examination showed a pale right optic disc, macular edema, and a cherry red spot. Optical coherence tomography done four hours after onset showed right acute cystoid macular edema and diffuse inner retinal thickening. Subsequent treatment with intravenous carbonic anhydrase inhibitor resulted in some visual improvement. Central retinal artery occlusion has been known to produce diffuse intraretinal edema instead of cystoids changes. We would like to discuss a case of acute cystoid macular edema in acute central retinal artery occlusion.

The outer and inner retinal function in patients with multiple evanescent white dot syndrome.

BACKGROUND: To investigate the outer and inner retinal function in patients with multiple evanescent white dot syndrome (MEWDS). METHODS: The retinal function of three subjects with MEWDS was investigated using one or a combination of full-field electroretinography (ERG), multifocal electroretinography (mfERG) or recording of multifocal oscillatory potentials (mfOP). RESULTS: In case 1, the scotopic, maximal, photopic and flicker ERG responses of the two eyes were similar but the amplitudes of the dark- and light-adapted OPs were markedly reduced in the affected eye. In cases 2 and 3, the ERG responses were grossly reduced in amplitude and as expected the OPs were also diminished. However, using the mfERG a residual area of 'normal' retinal function in the affected eye was identified. The local OP, assessed by the mfOP, within the residual 'normal' retinal area was reduced as compared with the corresponding retinal area of the fellow unaffected eye. Subsequently, the mfERG responses of the 'normal' retinal area were also reduced. CONCLUSION: The OPs were reduced throughout the retina in patients with MEWDS, even in the area with a normal mfERG. The electrophysiological findings suggest that functional abnormality in MEWDS may occur initially in the inner retina and subsequently involves the outer retina.

Diabetic retinopathy in diabetics referred to a tertiary centre from a nationwide screening programme.

INTRODUCTION: The aim of the study was to describe the prevalence and risk factors for diabetic retinopathy in a multi-ethnic diabetic patient cohort referred for retinal evaluation from a nationwide diabetic retinopathy screening programme in Singapore. MATERIALS AND METHODS: Seven hundred and forty-two patients, aged 21 to 95, referred for suspected diabetic retinopathy on annual one-field non-mydriatic 45 degree retinal photographs (Topcon TRC-NW6, Topcon Corporation, Tokyo, Japan) from primary care to the Singapore National Eye Centre diabetic retinopathy clinic were included. The photographs had been interpreted by 24 trained family physicians accredited every 2 years with a training programme. Patients underwent a standardised interview and examination. Fundi were examined with indirect ophthalmoscopy by 2 examiners. Presence and severity of diabetic retinopathy was graded into none, mild, moderate, severe, very severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Macular oedema and clinically significant macular oedema were also graded. RESULTS: Ninety-nine per cent of patients were type 2 diabetics. The prevalence of diabetic retinopathy was 38.1%, visionthreatening retinopathy was 11.8% and macular oedema was 6.9%. There were no racial differences. Significant predictors of any retinopathy were longer duration of diabetes, lower body mass index, being on treatment for hypertension, hypercholesterolaemia and use of diabetic medication. Predictors for vision-threatening retinopathy were younger age, longer duration of diabetes and lower body mass index. CONCLUSIONS: The use of one-field non-mydriatic 45 degree photography as a screening tool for diabetic retinopathy resulted in a cohort of which 38.1% had diabetic retinopathy. Risk factors for diabetic retinopathy of this cohort are also presented.

Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys.

Vascular endothelial growth factor (VEGF) is one of the major mediators of retinal ischemia-associated neovascularization. We have shown here that adeno-associated virus (AAV)-mediated expression of sFlt-1, a soluble form of the Flt-1 VEGF receptor, was maintained for up to 8 and 17 months postinjection in mice and in monkeys, respectively. The expression of sFlt-1 was associated with the long-term (8 months) regression of neovascular vessels in 85% of trVEGF029 eyes. In addition, it resulted in the maintenance of retinal morphology, as the majority of the treated trVEGF029 eyes (75%) retained high numbers of photoreceptors, and in retinal function as measured by electroretinography. AAV-mediated expression of sFlt-1 prevented the development of laser photocoagulation-induced choroidal neovascularization in all treated monkey eyes. There were no clinically or histologically detectable signs of toxicity present in either animal model following AAV.sFlt injection. These results suggest that AAV-mediated secretion gene therapy could be considered for treatment of retinal and choroidal neovascularizations.