A Novel Technique of Aseptic Manufacture of Autologous Serum Eye Drops (ASEDs) and Sterility Analysis of the Bottled Ophtioles.

PURPOSE: To introduce a novel technique of the aseptic manufacture of autologous serum eye drops (ASEDs) with a prefiltered closed system and to analyze the sterility of the produced ophtioles between 2018 and 2022. METHODS: This is a prospective single-center study conducted at the Department of Ophthalmology at a Swiss University Hospital between 2018 and 2022. For regulatory reasons, closed systems for manufacturing ASEDs are strongly recommended. We attached an upstream sterile filter (Sterivex PES0.22 µm Burlington, USA) to a commercially available closed system (COL System Modena, Italy) for manufacturing ASEDs. The goal of this novel approach was to reduce the microbiological contamination of the donated autologous blood. Using the presented manufacturing method, we are able to produce, on average, 56 ophtioles per batch, containing either 1.45 mL or 2.5 mL of autologous serum per ophtiole. For each batch of ASEDs, we performed a microbiological analysis by automated blood culture testing (BACTEC). This system examines the presence of bacteria and fungi. RESULTS: We analyzed all manufactured batches between 2018 and 2022. None of the 2297 batches and the resulting 129 060 ophtioles showed bacterial or mycotic contamination. During the analyzed period, two batches were discarded: one due to fibrin-lipid aggregations, further microbiological and histological work-up excluded any contamination; another due to false-positive HIV in serological testing. Overall, the contamination rate was 0%, and the batch discharge rate was 0.09%. CONCLUSIONS: The combination of upstream sterile filtration with a commercial closed system for manufacturing ASEDs proved to be effective in ensuring sterility without any contamination over the past 4 years. This is becoming crucial, as the demand for autologous blood products for treating ocular surface disorders, such as refractory dry eyes or nonhealing defects of the corneal epithelium, is on the rise.

Evaluation of Increase in Retinal Thickness as Diagnostic Marker in Central Artery Occlusion.

PURPOSE: To evaluate the increase in retinal thickness as a marker in predicting the onset of central retinal artery occlusions. METHODS: Retrospective clinical study conducted at one Swiss hospital. Electronic records were filtered for patients with artery occlusions. Optical coherence tomography data, including time between the imaging and ischemic event, were reviewed. Increase in relative retinal thickness was measured, defined as an increase in retinal thickness compared to the unaffected partner eye. This was correlated with the time from symptom onset. A cutoff value of relative increase of < 24.5% was applied, as suggested in previous studies. The results were compared to the time gathered from the electronic records, and sensitivity, specificity, positive predictive value as well as negative predictive value were calculated for predicting an ischemia time of < 4.5 h. RESULTS: Forty-two eyes from 41 patients with central artery occlusions were identified. Fourteen were female. Mean age was 66.4 ± 15.8 years. Initial corrected visual acuity was 2.41 ± 0.68 logMAR, and 2.13 ± 0.87 logMAR at the last follow-up (p > 0.05). Of eyes with a visual acuity of counting fingers (n = 38) or worse, 89.5% showed no improvement during follow-up, while eyes with logMAR 1 or better (n = 4) improved. Thirteen eyes (13 patients) presented within 4.5 h of the ischemic event. Four patients received i. v. thrombolysis, with visual recovery in one. In 12 eyes with an ischemia time of < 4.5 h, relative increase was below 24.5%. In the remaining 29 eyes with > 4.5 h, relative increase was below 24.5% in 4 eyes and above 24.5% in 25 eyes. This yielded a sensitivity of 92.3%, a specificity of 86.2%, with a positive predictive value of 75.0% and a negative predictive value of 96.2%. CONCLUSION: Central retinal artery occlusion is associated with severe vision loss. There is no current established therapy. Parameters that objectify the presence of a therapeutic window for thrombolysis are gaining in importance as patient history is often imprecise. Relative retinal thickness increase proved a noninvasive imaging parameter demonstrating adequate performance in detecting patients within the therapeutic window of thrombolysis. Further investigation of this parameter in central retinal occlusion is warranted.

Ophthalmological Outcomes in Patients with Susac Syndrome.

BACKGROUND: To report ophthalmological outcomes and treatment regimen in patients with Susac syndrome. METHODS: This is a retrospective analysis of patients with Susac syndrome treated between November 2015 and March 2023. Multimodal imaging findings, ophthalmic examination data, information on neurological and sensorineural involvement, and therapeutic regimen were reviewed. Visual acuity was recorded as the logarithm of the minimum angle of resolution (logMAR). Ophthalmological manifestations and disease severity were assessed using the previously described clinical activity score (CAS). RESULTS: Ten patients with Susac syndrome m : f = 5 : 5 were identified. The mean follow-up time was 31.2 ± 23.3 months (range 1 to 78 months). The mean age was 41.4 ± 13.8 years (range 21 to 59 years). At baseline, corrected distance visual acuity (CDVA) was 0.03 ± 0.08 logMAR. At the last follow-up, CDVA improved to 0.00 ± 0.03 logMAR (p = 0.029). Three of 20 eyes showed an improvement of 5 letters, while no loss of visual acuity was recorded during the follow-up time. Baseline CAS was 10.65 ± 12.69, and CAS at the last follow-up was 5.15 ± 5.49 (p = 0.068). Except for one patient, all were initially treated with intravenous (i. v.) steroids and subsequent oral tapering. Depending on the treatment response, cyclophosphamide (n = 4), i. v. immunoglobulins (IVIGs) (n = 4), anti-CD20 antibodies (n = 3), or plasmapheresis (n = 1) were applied. All patients under treatment for more than 1 month (n = 9) showed improvement in CAS and CDVA. CONCLUSION: Susac syndrome is a rare autoimmune vascular endotheliopathy. Treatment of Susac syndrome appears to result in improving CAS and CDVA. The majority of patients, in addition to the systemic steroids, required systemic immunosuppressive agents. Interdisciplinary communication is crucial to reduce the time to diagnosis and initiation of therapy in patients with Susac syndrome.

Imaging Assessment of Peripapillary Vessel Diameters in Postmortem Eyes.

PURPOSE: Proof of concept of ex vivo retinal vessel diameter measurements in human postmortem eyes. METHODS: En face near-infrared (IR) images and optical coherence tomography (OCT) of the optic nerve head (ONH) were captured ex vivo with a Heidelberg Engineering Spectralis (Spectralis, version 7.0.4, Image Capture Module, version 1.2.4, Heidelberg Heidelberg, Germany) device, using a custom-made eye chamber holding and positioning the eyes during the image process. Thirty-two formaldehyde-fixated eyes of 16 patients were imaged. In the IR images, two independent graders measured retinal vessel diameters at the intersection of a drawn circle centered on the ONH with diameters of 2.0 mm and 3.4 mm, respectively. The anatomically corresponding measurements between both graders were statistically analyzed using a Wilcoxon signed-rank test. RESULTS: A total of 246 matched measurements of both graders were analyzed across all 32 imaged eyes. Statistically significant differences between the graders were found for arterioles at 2 mm from the ONH. The other measurements did not show statistically significant intergrader differences. The mean values for arteriole diameters were 72.2 µm at 2.0 mm and 61.5 µm at 3.4 mm for grader 1, and 66.4 µm at 2.0 mm and 63.2 µm at 3.4 mm for grader 2. The mean diameter for venules were 75.5 µm at 2.0 mm and 79.3 µm at 3.4 mm for grader 1, and 67.4 µm at 2 mm and 79.1 µm at 3.4 mm for grader 2. CONCLUSION: To the best of our knowledge, this is the first study to present IR image-based retinal vessel diameters in ex vivo postmortem eyes. Retinal IR/OCT imaging is possible, and measurements are reproducible in formaldehyde-fixated human eyes. Fixation artefacts result in lower image quality, and this can impose challenges in correctly detecting, classifying, and measuring retinal vessels.

OUTCOMES OF SWITCHING FROM PROACTIVE TO REACTIVE TREATMENT AFTER DEVELOPING ADVANCED CENTRAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We assessed outcomes of eyes with neovascular age-related macular degeneration (nAMD) that switched from proactive (treat-and-extend) to reactive (pro re nata) treatment regimen after developing macular atrophy (MA) or submacular fibrosis (SMFi). METHODS: Data were collected from a retrospective analysis of a prospectively designed, multinational registry of "real-world" nAMD treatment outcomes. Eyes without MA or SMFi when starting treatment with a vascular endothelial growth factor inhibitor regimen that subsequently developed MA or SMFi were included. RESULTS: Macular atrophy developed in 821 eyes and SMFi in 1,166 eyes. Seven percent of eyes that developed MA and 9% of those that developed SMFi were switched to reactive treatment. Vision was stable at 12 months for all eyes with MA and inactive SMFi. Active SMFi eyes that switched to reactive treatment had significant vision loss. No eyes that continued proactive treatment developed ≥15 letter loss, but 8% of all eyes that switched to a reactive regimen and 15% of active SMFi eyes did. CONCLUSION: Eyes that switch from proactive to reactive treatment after developing MA and inactive SMFi can have stable visual outcomes. Physicians should be aware of the risk of a significant loss of vision in eyes with active SMFi that switch to reactive treatment.

Twenty-four-month real-life treatment outcomes of polypoidal choroidal vasculopathy versus type 1 macular neovascularization in Caucasians.

BACKGROUND: To compare 24-month real-world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population. METHODS: Retrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment-naïve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24-month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti-VEGF injections, time to lesion inactivation and proportion of active visits. RESULTS: A total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p = 0.95). Adjusted VA change at 2 years was higher in PCV (mean [95% CI], +1.2 [-1.6, 4.1] vs. -3.6 [-6, -1.2] letters, p = 0.005). PCV received fewer anti-VEGF injections over the first 24 months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p = 0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343] days, p = 0.04) and was less frequently graded 'active' (62% vs. 68% of visits, p = 0.001). CONCLUSIONS: PCV had slightly better VA outcomes over 24 months of treatment than type 1 MNV after receiving less anti-VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians.

Severe Complications after Corneal Collagen Cross-Linking (CXL).

PURPOSE: To present a case series of rare and severe complications after corneal collagen cross-linking (CXL) of keratoconus patients. METHODS: Single-center descriptive case series covering the period of 2012 to 2022 at the Department of Ophthalmology at the University Hospital, Zurich, Switzerland. RESULTS: We present four eyes of four patients that showed severe unusual complications within the first month after CXL. Three patients had been treated with the classical epithelium-off "Dresden" protocol. One patient had been treated with the accelerated epithelium-off protocol. One patient presented with extensive corneal edema due to rubbing the eye after treatment. Two patients showed a bacterial infectious keratitis: one due to Streptococcus pneumoniae and the other due to Staphylococcus hominis, Micrococcus luteus, and Streptococcus epidermidis. The latter of the two patients exhibited extensive infectious crystalline keratopathy. The fourth patient showed a severe ulcerative lesion where no infectious cause could be found. Therefore, an autoimmune keratolytic process had to be suspected. Apart from the corneal edema, which resolved ad integrum, the other complications resulted in permanent corneal scarring and thinning. One patient needed an emergency amniotic transplant. CONCLUSION: Severe complications after CXL remain rare. Most common causes are complications that are not directly associated with the treatment as such. Those indirect complications occur after the treatment during the healing course of the epithelium. Associations with bandage contact lenses, topical steroids, atopic disease, and inappropriate patient behavior are often suspected. Correctly performed corneal scrapings with repeated microbiological analysis and a detailed patient history are essential for establishing the correct diagnosis, especially in complicated cases that do not respond to a standard therapeutic regimen. This case series supports the efforts that are currently taken to improve the CXL technique in a way that postoperative complications are further reduced. A more efficient epithelium-on technique might be a step in that direction.

Natural Course of Solar and Laser-Associated Retinal and Macular Injuries at a Primary Care Hospital in Switzerland.

BACKGROUND: Solar and laser-associated retinopathies are rare occurrences. The two retinopathies are both photo-induced but differ in the involved intensity and duration of exposure. The purpose of this study was to evaluate the clinical features and natural course of these two entities, with a focus on the changes in the outer retina over time. PATIENTS AND METHODS: This retrospective analysis assessed patients with solar or laser maculopathy seen at the Department of Ophthalmology of the University Hospital Zurich in Switzerland over the last 10 years. Visual acuity (VA; Snellen) and optical coherence tomography (OCT) findings were reviewed and analyzed at baseline and last follow-up visit. Areas of damaged outer retina, identified on en face OCT images as hyporeflective areas, were tagged and compared between visits. Descriptive analysis was performed by calculating mean values ± standard deviation (SD). Statistical evaluation was done using the Wilcoxon signed rank test. A p value < 0.05 was considered statistically significant. RESULTS: Five patients with solar retinopathy and six patients with laser-associated retinopathy were identified. In the solar retinopathy group, mean VA at baseline was 0.80 (SD ± 0.37) and improved to 0.90 (SD ± 0.36). This was not statistically significant (p = 0.066). In the laser-associated retinopathy group, mean VA at baseline was 0.89 (SD ± 0.18) and improved to 1.03 (SD ± 0.09), which was not statistically significant either (p = 0.063). At baseline, in OCT cross-sections, initial changes were observed in the interdigitation, myoid, and ellipsoid zone, as well as the outer nuclear layer and the Henle fiber layer. At follow-up, most cases presented an alteration in the residual ellipsoid zone, with the degree of the aforementioned alterations depending on the size of the initial defect. A decrease of the hyporeflective alterations measured in en face OCT scans was observed in both groups but was only statistically significant in the laser-associated retinopathy group (p = 0.018 versus p = 0.172). CONCLUSIONS: OCT can help to detect and monitor solar and laser-associated retinal injuries. Most injuries are minor, with good functional restitution. Minor changes in the ellipsoid zone often persist, even in cases with full visual recovery.

OUTCOMES OF RETROPUPILLARY IRIS CLAW INTRAOCULAR LENS IMPLANTATION COMBINED WITH PARS PLANA VITRECTOMY.

PURPOSE: To report 12-month visual outcomes, incidence of intraocular pressure (IOP) changes and postoperative complications after pars plana vitrectomy with retropupillary implantation of an iris claw intraocular lens (IOL) in aphakic eyes after complicated cataract surgery and eyes with a dislocation of the IOL. METHODS: This is a retrospective analysis of eyes undergoing implantation of an iris claw IOL combined with pars plana vitrectomy from 1st of January 2009 until 30th of June 2018 after complicated cataract extraction with capsular loss (Group A) or dislocation of an IOL (Group B). Corrected distance visual acuity was analyzed in logarithm of the minimum angle of resolution (logMAR) units, IOP was recorded in mmHg. RESULTS: Eyes in Group A (n = 49) improved from a preoperative median visual acuity of 0.523 logMAR (Snellen 20/65) to 0.201 logMAR (Snellen 20/30), P < 0.01. Eyes in Group B (n = 126) showed stable median visual acuity, preoperative 0.301 logMAR (Snellen 20/40) versus postoperative 0.222 logMAR (Snellen 20/30), P > 0.05. During 12 months in Group A, IOP >21 mmHg occurred in 9 (18.4%) eyes; no eye had an IOP <6 mmHg. In Group B, IOP >21 mmHg occurred in 15 (11.9%) eyes, IOP <6 mmHg in 5 (4%) cases. None of the eyes in Group A and B had IOP >21 mmHg or <6 mmHg at 12 months follow-up. CONCLUSION: The retropupillary implantation of an iris claw IOL with pars plana vitrectomy provides adequate visual rehabilitation and seems to be safe in IOP changes.

THE IMPACT OF DISEASE ACTIVITY ON 5-YEAR OUTCOMES IN PATIENTS UNDERGOING TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the impact of disease activity on clinical outcomes in a "real-world" cohort with neovascular age-related macular degeneration over 5 years. METHODS: Data were obtained from the prospectively defined Fight Retinal Blindness! registry. Eyes were divided into tertiles based on the proportion of visits where choroidal neovascular lesion was active (low, moderate, and high) up until 5 years. RESULTS: Data from 2,109 eyes were included. The adjusted mean (95% confidence interval) visual acuity change was -0.5 letters (-1.8 to 1.1), 1.8 letters (0.2 to 3.4), and -2.5 letters (-4.2 to -1.3) in the low, moderate, and high activity groups respectively, P < 0.001. Eyes in the low activity group were more likely to develop macular atrophy (56, 47 and 26% in the low, moderate, and high activity groups respectively, P < 0.001) but less likely to develop subretinal fibrosis (27, 35 and 42% in the low, moderate, and high activity groups respectively, P < 0.001). CONCLUSION: Eyes with higher and lower levels of disease activity had poorer outcomes than eyes with moderate activity over 5 years, apparently because of the development of subretinal fibrosis or macular atrophy.

THREE-YEAR TREATMENT OUTCOMES OF AFLIBERCEPT VERSUS RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: Data from the Fight Retinal Blindness! Registry.

PURPOSE: Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. METHODS: This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. RESULTS: We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. CONCLUSION: Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

INTERNATIONAL IMPACT OF THE COVID-19 PANDEMIC LOCKDOWN ON INTRAVITREAL THERAPY OUTCOMES: Fight Retinal Blindness Registry.

PURPOSE: To evaluate the impact of the COVID-19 pandemic lockdowns on the outcomes of eyes treated for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion in eight countries. METHODS: A multicenter international database study of 5,782 eyes (4,708 patients) receiving intravitreal antivascular endothelial growth factor injections before, during, and after national lockdowns. The baseline visit was defined as the last visit within 3 months before lockdown, and prelockdown and postlockdown periods were defined as 6 months before and after the lockdown date. RESULTS: Eyes with neovascular age-related macular degeneration (n = 4,649) lost vision in all countries in proportion to the reduced number of injections. The mean visual acuity change postlockdown ranged from -0.4 to -3.8 logarithm of the minimum angle of resolution letters, and the median number of injections/visits decreased from 4-5/4-7 to 2-4/2-4 postlockdown. The diabetic macular edema (n = 654) and retinal vein occlusion (n = 479) eyes' mean visual acuity change ranged from -2.8 to +1.7 letters and -1.6 to +0.1 letters, and the median number of injections/visits decreased from 2.5-5/4-6 to 1-3/2-4 and from 3-5.5/4-5 to 1-3.5/2-3.5, respectively. The 6-month dropout rates postlockdown were 20% for neovascular age-related macular degeneration, 27% for diabetic macular edema, and 28% for retinal vein occlusion. CONCLUSION: This international study provides estimates of the impact of COVID-19 pandemic lockdown on intravitreal therapy and suggests that prioritizing neovascular age-related macular degeneration eyes seems appropriate.

One-year real-world outcomes of bevacizumab for the treatment of macular oedema secondary to retinal vein occlusion.

BACKGROUND: Bevacizumab is the only agent that many people can afford, yet there are only limited data on whether it improves macular oedema (MO) secondary to retinal vein occlusion (RVO) in real-world clinical practice. Here we studied 12-month real-world treatment outcomes of bevacizumab for RVO-related MO. METHODS: This was a multicentre, observational study analysing 12-month data from the Fight Retinal Blindness! (FRB) database. We studied treatment-naïve eyes with MO secondary to RVO commencing bevacizumab therapy between June 2009 and June 2019. Visual acuity (VA) and central subfield thickness (CST) were measured at baseline, 6 and 12 months. The primary outcome was a change in VA from baseline to 12 months. RESULTS: Two hundred and twenty treatment naive eyes were analyzed. The baseline VA for BRVO was better than CRVO (55.8 vs. 42.6 LogMAR letters) and this gap widened over the 12-month period, with a 12-month VA change of +14.0 (95% CI 11.1, 16.8) letters for BRVO and + 11.9 (95% CI 6.4, 17.4) for CRVO. The mean CST at baseline was 511 µm for BRVO and 627 µm for CRVO, falling at 12 months by -155 µm (-190, -121) in BRVO and -198 µm (-252, -145) in CRVO. The median number of injections for BRVO and CRVO completers was 7 (5, 9). CONCLUSIONS: Bevacizumab can be an effective treatment of RVO-MO in a real-world setting with outcomes approaching those reported by the seminal clinical trials. The functional and anatomical outcomes of intravitreal therapy were better for BRVO than CRVO.

Differences in Mean Values and Variance in Quantitative Analyses of Foveal OCTA Imaging.

PURPOSE: Multiple approaches for quantifying parameters such as vessel density (VD) and vessel length density (VLD) in optical coherence tomography angiography (OCTA) en-face segmentations are currently available. While it is common knowledge that data gathered from different methods should not be directly compared to each other, a comparison of the different methods can help to further the understanding of differences between different methods of measurement. Here we compare a common method of semiautomatically quantifying VD and VLD with an automated method supplied by the manufacturer of an OCTA device and report on differences in performance in order to probe for and highlight differences in values gathered by both methods. METHODS: OCTA was performed using the swept source PLEX Elite 9000 device, software version 2.0.1.47652 (Carl Zeiss Meditec Inc., Dublin, CA, USA). Scans of 3 mm × 3 mm from healthy volunteers centred on the fovea were acquired by a well-trained certified ophthalmologist. Scans with a signal strength of 8 out of 10 or higher were included. Quantitative parameters of the 3 mm × 3 mm cube scans were automatically generated and segmented into superficial capillary plexus (SCP) and deep capillary plexus (DCP) layers using layer segmentation produced by the instrument software and prototype analysis VD quantification software (Macular Density v.0.7.1, ARI Network Hub, Carl Zeiss Meditec Inc., Dublin, CA, USA) supplied by the manufacturer. An alternative approach of quantitative analysis of VD and VLD was performed manually with ImageJ (National Institutes of Health, Bethesda, Maryland, USA), as previously reported. VD was assessed as the ratio of the retinal area occupied by vessels. VDL was measured as the total length of the skeletonised vessels using 1-pixel centre line extraction of the blood vessels. RESULTS: We report differences in standard deviation (SD) in OCTA parameters obtained using different methods. The standard deviation of VD and VLD measurements was statistically significantly different in VD of 3 mm × 3 mm DCP (p = 0.009), VLD of 3 mm × 3 mm SCP (p = 0.000), and VLD of 3 mm × 3 mm DCP (p = 0.021). No statistically significant differences were found in VD of 3 mm × 3 mm SCP (p = 0.128) or VLD of 3 mm × 3 mm SCP (p = 0.107). CONCLUSIONS: As expected, we were able to demonstrate significant differences in quantitative OCTA parameters gathered from the same images using different methods of quantification. Values gathered using different methods are not interchangeable. In scientific studies and in situations where long-term follow-up is necessary, the same device and the same method of quantification should be used to maintain retrospective comparability of measurements.

Treat-and-extend versus fixed bimonthly treatment regimens for treatment-naive neovascular age-related macular degeneration: real world data from the Fight Retinal Blindness registry.

PURPOSE: To compare the outcomes of two different antivascular endothelial growth factor treatment regimens for treatment-naive eyes with neovascular age-related macular degeneration in routine clinical care at 12 and 24 months in Spain. METHODS: Observational study using the Fight Retinal Blindness (FRB) outcomes registry platform. Eyes were treated with fixed bimonthly (FB) aflibercept group at one center and a treat-and-extend (TAE) regimen using either aflibercept or ranibizumab at the other center. RESULTS: We included 192 eyes. Of these, 160 eyes (83%) completed 12 months (86 TAE and 74 FB) and 79 (41%) completed 24 months (46 for TAE and 33 for FB) of follow-up. No statistically significant differences (p > 0.05) were found regarding mean visual acuity (VA, logMAR letters) at baseline (12 month cohort TAE 59.6 vs FB 57.9; 24 month cohort TAE 61.7 vs FB 62.6), final mean VA (12 month cohort TAE 61.1 vs FB 63.0; 24 month cohort TAE 64.8 vs FB 66.4), and median number of injections (12 months TAE 7 vs FB 7; 24 months TAE 11 vs FB 12). However, the distribution of injection frequencies for the TAE group was larger, with 35% of TAE eyes receiving ≤ 6 injections at 12 months compared with only 19% of FB eyes (p = 0.024). CONCLUSION: Similar VA results were observed with TAE and FB regimens, with no differences in the median number of injections. However, the TAE approach seemed to deliver a wider distribution of injection frequencies due to its individualized approach, which may help reduce the burden of injections in some eyes.

FIVE-YEAR INCIDENCE AND VISUAL ACUITY OUTCOMES FOR INTRAVITREAL THERAPY IN BILATERAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Fight Retinal Blindness! Project.

PURPOSE: To compare treatment intensity and mean visual acuity gains for first- and second-affected eyes with age-related macular degeneration nAMD over 5 years of treatment. The cumulative incidence of second-eye involvement was assessed. METHOD: We analyzed data from the Fight Retinal Blindness! project database, a prospectively designed registry of "real-world" outcomes from Australia, New Zealand, Switzerland, and Singapore. Patients with bilateral age-related macular degeneration with ≥5 years of follow-up on treatment were included. RESULTS: Six thousand five hundred and forty-two eyes being treated for age-related macular degeneration were tracked from 2005 to 2017. Thousand two hundred and sixty-one patients had bilateral age-related macular degeneration; of whom, 302 had 5 years of follow-up. Of these, 170 patients started treatment for each eye at least 2 months apart. The mean baseline visual acuity of second-affected eyes was significantly higher than that of first-eyes (20/50 + 2 vs. 20/80; P < 0.01). Second-affected eyes lost a mean of 5.8 (-9.1 to -2.6) logarithm of the minimum angle of resolution letters after 5 years of treatment, whereas the vision of the first-affected eyes remained stable (P = 0.01). Second-affected eyes received fewer injections than the first-affected eyes after the first year of treatment (6.2/year vs. 7.8/year; P < 0.01) and reactivated earlier (376 vs. 507 days; P = 0.04). The cumulative incidence of second eye involvement was 54% over 5 years. CONCLUSION: Second-affected eyes received fewer treatments and reactivated earlier. Care should be taken to avoid undertreating second-affected eyes.

ASSOCIATION BETWEEN ANATOMICAL AND CLINICAL OUTCOMES OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: Assess the relationship between subretinal fluid (SRFL), intraretinal fluid, and visual outcomes of neovascular age-related degeneration in routine clinical practice. METHODS: Treatment-naive eyes enrolled in the Fight Retinal Blindness! registry after January 2017 were identified. Lesion activity was graded at each visit as inactive, active not SRFL only (A-NSRFL only), or active SRFL only (A-SRFL only). Eyes were grouped based on initial activity as follows: 1) initially A-NSRFL only or 2) initially A-SRFL only, and their predominant activity status over 12 months was as follows: 1) mostly inactive, 2) mostly A-NSRFL only, or 3) mostly A-SRFL only. RESULTS: Seven hundred and three eyes were eligible for analysis. Initially A-NSRFL only had a similar adjusted mean 12-month visual acuity change to initially A-SRFL eyes (5.7 vs. 6.9 letters; P = 0.165), but their final visual acuity was worse (62.5 vs. 67.5 letters at 12 months; P = 0.003). The adjusted mean 12-month visual acuity change between the predominant activity groups was significantly different (P = 0.005), with mostly inactive (7.6 letters) and mostly A-SRFL only (7.5 letters) eyes gaining more than mostly A-NSRFL only eyes (3.6 letters). CONCLUSION: Eyes with SRFL only had similar outcomes at 1 year to eyes that were mostly inactive. Intraretinal fluid was associated with worse visual outcomes, highlighting the importance of distinguishing between intraretinal fluid and SRFL when managing neovascular age-related degeneration.

Neovascular age-related macular degeneration: A review of findings from the real-world Fight Retinal Blindness! registry.

The use of vascular endothelial growth factor (VEGF) inhibitors has revolutionised the treatment of neovascular age-related macular degeneration (nAMD) since the pivotal Phase III studies demonstrated their efficacy more than 10 years ago. The Fight Retinal Blindness! project was developed to track the treatment outcomes of patients with nAMD in real-world practice. Data from this registry have been used to answer several clinically relevant questions related to the treatment of nAMD including the effect of under-treatment, the comparative effectiveness of different anti-vascular endothelial growth factor agents, long-term treatment outcomes, identifying optimal treatment regimens and the rate and outcomes of rare adverse events. Observational studies are a valuable complement to the shortcomings of clinical trials and a combination of data from real-world settings and clinical trials are necessary to provide evidence on how to achieve the best outcomes for individual patients with nAMD.

Neovascular age-related macular degeneration at treatment intervals of 14 weeks or greater.

BACKGROUND: We assessed the proportion of eyes with neovascular age-related macular degeneration (nAMD) in routine clinical practice that reach ≥14 week treatment intervals and their outcomes. METHOD: We analysed data from the Fight Retinal Blindness! (FRB!) Project database, a prospectively designed registry of 'real-world' outcomes. Treatment-naive eyes starting vascular endothelial growth factor (VEGF) inhibitors for nAMD from 1st January 2006 were included. Eyes were defined to have reached the ≥14 week treatment interval if they received ≥2 consecutive injections at treatment intervals of ≥14 week but not exceeding 26 weeks. Outcomes were reported in a subgroup of eyes that had 12 months of follow-up from reaching this interval. RESULTS: Of the 3907 treatment-naïve eyes that started treatment during the identified periods on a treat-and-extend regimen and received at least 8 injections over the first 2 years, 402 (10%) eyes received at least 2 consecutive injections at an interval of ≥14 week during their follow-up. Fifty-two percent of these eyes maintained vision to 12 months, however only 40% stayed at this interval and 25% of the lesions reactivated. CONCLUSION: We found that only 10% of eyes with nAMD were extended beyond a 13-week injection interval and that over half had returned to a shorter interval by 12 months. Eyes that stayed at this extended treatment interval maintained stable vision. More data on the outcomes of eyes treated with intervals longer than 3 months are required to establish whether emerging VEGF inhibitors provide a more sustained effect than the currently available drugs.

Thermal Laser Monotherapy for Extrafoveal Polypoidal Choroidal Vasculopathy.

INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid. Diagnosis is mainly based on polypoidal aneurysm-like lesions seen in indocyanine green (ICG) angiography. Various therapeutic options have been proposed. METHODS: Outcomes of 10 cases with extrafoveal PCV and consecutive macular edema treated with thermal laser are reported. Diagnosis of PCV was confirmed by ICG angiography. RESULTS: Upon successful occlusion of the polyps in 10 eyes after thermal laser treatment demonstrated in ICG angiography, a regression of central foveal edema was seen in optical coherence tomography and color fundus photography. Visual acuity improved from logMAR 0.8 to logMAR 0.3. Follow-up ranged from 4 months to 15 years, with a median of 1 year. Two eyes had a recurrence of exudative maculopathy 5 and 7 years after laser treatment, respectively. CONCLUSION: A careful differentiation between various subforms of exudative maculopathy using fluorescein and ICG angiography can identify certain selected patients with extrafoveal PCV, for whom thermal laser monotherapy can be a therapeutic option.