CORRELATION BETWEEN INFLAMMATORY FOCI REACTIVATION AND ATROPHY GROWTH IN EYES WITH IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To correlate the number of inflammatory reactivations in atrophic foci of multifocal choroiditis (MFC) with their growth rate over a 4-year span. METHODS: Comparative case series. Optical coherence tomography scans of patients affected by MFC were reviewed to identify reactivations within or at the margin of atrophic MFC foci. The area of selected lesions was semiautomatically delineated on fundus autofluorescence images and recorded at yearly intervals for a total follow-up of 4 years. The main outcome was the difference in annual square-root transformed area growth rate between lesions that reactivated and lesions that did not. RESULTS: Sixty-six foci of 30 eyes of 24 patients were included. All MFC foci enlarged over time, but the annual growth rate was more than double in lesions that reactivated compared with those that did not (mean [SD], 0.051 [0.035] vs. 0.021 [0.015] mm/year, P < 0.001), despite starting from comparable baseline areas. For each additional inflammatory reactivation, the annual growth rate increased by more than 20% (+0.009 mm/year, 95% CI [0.006, 0.012], P < 0.001). CONCLUSION: Increasing number of reactivations of atrophic foci led to proportional increments in their growth rate, highlighting the need for a tight control of inflammatory relapses in patients affected by MFC.

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.

Quantitative autofluorescence findings in patients undergoing hydroxychloroquine treatment.

BACKGROUND: To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects. METHODS: Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAF8 ). RESULTS: Thirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p = 0.004). Although HCQ patients showed a higher mean qAF8 compared with untreated subjects (294.7 ± 65.3 vs. 268.9 ± 57.5), the difference was not significant (p = 0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared with untreated subjects (all p < 0.05). CONCLUSIONS: These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.

OPTICAL COHERENCE TOMOGRAPHY FEATURES OF CHOROIDAL NEOVASCULARIZATION AND THEIR CORRELATION WITH AGE, GENDER, AND UNDERLYING DISEASE.

PURPOSE: To investigate the influence of age, gender, and underlying disease on the optical coherence tomography (OCT) features of choroidal neovascularization (CNV) secondary to inflammation, myopia (mCNV), and age-related macular degeneration (AMD-CNV). METHODS: Demographic and clinical data of eyes with treatment-naive inflammatory CNV, mCNV, and Type 2 AMD-CNV were collected. Optical coherence tomography images were reviewed to determine the presence of pitchfork sign, pigment epithelial detachment, subretinal fluid (SRF), intraretinal cysts, subretinal hyperreflective material, atrophy, and outer retinal disruption graded 1 to 4. The influence of demographics and underlying etiology on OCT signs was investigated. RESULTS: One hundred and eighty-five eyes from 179 patients were enrolled. The mean [SD] age was 36 [±14.4], 62 [±18], and 77 [±8] for the inflammatory CNV, mCNV, and AMD-CNV, respectively (P < 0.001). Multiple linear regression showed that the presence of pitchfork sign was negatively associated with age (P < 0.0001), regardless of underlying disease. By contrast, the SRF, pigment epithelial detachment, intraretinal cysts, and the outer retinal disruption were all positively influenced by age, regardless of gender and underlying disease (all P < 0.01). Logistic regression showed that none of the OCT signs increased the likelihood for diagnosis of inflammatory CNV. By contrast, the absence of SRF was suggestive for mCNVs, and the presence of pigment epithelial detachment and SRF was suggestive for AMD-CNVs. CONCLUSION: The age of the patient had a significant effect on the OCT appearance of the CNV, particularly the presence of a pitchfork sign, regardless of the underlying etiology. The absence of SRF was suggestive for a diagnosis of mCNVs. The presence of SRF and pigment epithelial detachment was suggestive for AMD-CNVs.

Performance outcomes from a DMEK peeling and preparation wet lab.

OBJECTIVE: To evaluate the Descemet membrane endothelial keratoplasty (DMEK) preparation performance of trainee surgeons in an ex vivo human donor cornea DMEK wet lab simulation setting. METHODS: Human donor corneoscleral rims unsuitable for transplantation were obtained from Moorfields Lions Eye Bank. At the wet lab, graft stripping was performed by scoring the peripheral endothelium. The trypan blue positive cells (TBPC) and cell density (cells/mm2-reticule count) were counted manually before and after stripping. The procedural time, peripheral and central tears and complete peel-off were also recorded and analysed. RESULTS: Eight trainee surgeons attended the wet lab each attempting three DMEKs. Between the first and last attempts a significant decrease was seen in the procedural time (17.6 min vs 10.6 min (p<0.05)) and the TBPC % (12.9% vs 3.8% (p<0.05)). The percentage of tears peripherally and centrally also reduced between the first and the last trials (50% vs 13% (p=0.2226) and 38% vs 0% (p=0.1327)). A significant correlation was found between longer peeling times and higher TBPC % (p<0.001) with a 0.7% endothelial mortality increase for each additional minute required to complete the peel. CONCLUSIONS: DMEK wet labs provide a controlled risk-free learning opportunity for trainee surgeons to improve confidence and competence. Wet labs improve the success rate of DMEK graft preparation as well as flatten the learning curve. This emphasises the importance of continued support for the expansion of this valuable learning resource, promoting wider uptake of DMEK surgery.

Comparative Analysis of Tomographic Indicators Forecasting Decompensation in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To compare the performance of 3 commercially available tomographers (the Pentacam Scheimpflug camera, the swept-source optical coherence tomography Casia, and the blue light slit-scanning tomographer Precisio) in the identification of patterns associated with Fuchs endothelial corneal dystrophy (FECD) decompensation. METHODS: This was a clinic-based cross-sectional imaging study. Pachymetry maps and posterior surface elevation maps were acquired with the 3 devices from 61 eyes affected by FECD. The maps were graded according to the evidence of tomographic patterns predictive of FECD decompensation (loss of parallel isopachs, displacement of the thinnest point, and focal posterior depression) by 2 blind cornea specialists. RESULTS: The loss of parallel isopachs was significantly less frequently evident in Pentacam pachymetry maps [8%, 95% confidence interval (CI) (3%, 18%)] compared with both the Casia [31%, 95% CI (20%, 44%), P = 0.01] and Precisio devices [24%, 95% CI (15%, 37%), P = 0.05]. The displacement of the thinnest point was graded as most evident in a significantly higher proportion of Precisio pachymetry maps [43%, 95% CI (31%, 55%)] compared with both the Pentacam [13%, 95% CI (6%, 24%), P = 0.001] and Casia devices [21%, 95% CI (12%, 33%), P = 0.03]. There were no significant differences in the identification of focal posterior depression on posterior elevation maps across the 3 devices. CONCLUSIONS: Identification of patterns predictive of FECD prognosis on pachymetry and posterior elevation maps is possible with different devices. However, their evidence varies across tomographers, and the results from different devices are not interchangeable.

Open-source, 3D printable IOL holder for detailed, smartphone-based anterior segment photography.

Smartphones are increasingly relevant resources in medical practice as they are ubiquitous and reasonably cheap. Among the advantages of using smartphones in medical practise, there is the possibility of obtaining reproducible photographic documentation of various conditions. This is particularly true in the ophthalmic field, where anterior segment color photography plays a significant role in the diagnosis and the management of ocular surface diseases. Here we propose an original design for an open-source smartphone accessory for taking and sharing high-definition photographs of the anterior segment. It can be easily reproduced via 3D printing, and it only needs to be integrated with an intraocular lens (IOL), widely available to the majority of ophthalmologists. Compared to other solutions described previously, it allows a precise and reproducible placement of the IOL on the smartphone camera, avoiding manual positioning that could result tricky and time-consuming. The IOL holder is cheap, scalable, portable and it can be quickly assembled and disassembled, without permanently modifying the smartphone camera.

Double trouble in DMEK surgery: Learning experience and review of the literature.

PURPOSE: To report a challenging Descemet Membrane Endothelial Keratoplasty (DMEK) case, complicated by intraoperative aqueous misdirection and spontaneous anterior chamber fibrin reaction. METHODS: A 70-year-old female affected by corneal edema due to Fuchs endothelial dystrophy underwent a triple procedure (cataract extraction - IOL implantation - DMEK surgery) in her left eye. This report illustrates the management of the intraoperative complications of aqueous misdirection syndrome and anterior chamber fibrin reaction. RESULTS: Despite the optimal management of the posterior pressure and the thorough removal of the fibrinous reaction during the case, the DMEK graft was not completely unfolded and centred at the end of the surgical procedure. Nonetheless, the patient showed good long-term anatomical and functional recovery: at the last follow-up (2 years after surgery), central corneal thickness was 526 µm with a best corrected visual acuity of 20/25 and an endothelial cell density of 1112 cell/mm2. CONCLUSION: Early recognition and prompt management of intraoperative aqueous misdirection syndrome and anterior chamber fibrin reaction during DMEK surgery is essential to ensure good functional and anatomical outcomes.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

Quality assurance in corneal transplants: Donor cornea assessment and oversight.

The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.

Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis.

PURPOSE: To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. DESIGN: Multicenter retrospective matched cohort study. METHODS: Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. RESULTS: A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). CONCLUSIONS: IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.

Topical Antiseptics in Minimizing Ocular Surface Bacterial Load Before Ophthalmic Surgery: A Randomized Controlled Trial.

PURPOSE: To investigate the reduction of the ocular surface bacterial load induced by 2 commercially available ophthalmic antiseptic formulations, povidone-iodine (PVI) 0.6% and chlorhexidine (CLX) 0.02%, before ocular surgery. DESIGN: Randomized controlled trial. METHODS: Seventy adult patients undergoing intraocular surgery (phacoemulsification) were randomized to receive in the index eye PVI (group A) 4 times a day for 3 days or CLX (group B) 4 times a day for 3 days before surgery. The untreated eye was used as control. A conjunctival swab was taken in both eyes before (T0) and after (T1) therapy. Microbial DNA was quantified with real-time polymerase chain reaction (PCR) analysis. The Mick algorithm was used to compare the abundance of each genus/genera against the distribution of abundances from the reference. At T1, patients filled a questionnaire to evaluate therapy-induced symptoms. Primary outcome was the reduction of bacterial DNA at T1 (microbial load), vs control arm, expressed as mean number of real-time PCR cycle times (CTs). Secondary outcomes were taxonomic composition, differential abundance, and therapy-induced ocular symptoms. RESULTS: The T0-T1 difference in CT was significant in group B, but not in group A (mean [95% CI], 0.99 [0.33] vs 0.26 [0.15], P < .001, and 0.65 [0.3] vs 0.45 [0.41], P = .09, respectively). The taxonomic composition, alpha, and beta diversity remained consistent at all time points in both groups. The rate of patients reporting therapy-induced ocular symptoms and the mean discomfort grade were greater in group A than in group B (97% vs 26% and 4.97±2.48 vs 0.66±1.53, respectively). CONCLUSIONS: Compared with PVI 0.6%, CLX 0.02% induced a greater reduction of ocular surface bacterial load, with no significant alterations of the taxonomic composition. Moreover, CLX was better tolerated than PVI.

Effect of Low-Temperature Preservation in Optisol-GS on Preloaded, Endothelium-Out DMEK Grafts.

The aim of the study was to assess different temperature ranges for the preservation of pre-loaded Descemet Membrane Endothelial Keratoplasty (DMEK) grafts in the DMEK RAPID Mini device. METHODS: Three groups of 15 DMEK grafts (five per group) were pre-loaded in the DMEK RAPID Mini and preserved in Optisol-GS for 72 h at different temperatures: group A at >8 °C, group B between 2-8 °C and group C at <2 °C. After stripping and preservation, the viability of the endothelium, cell loss and morphology were assessed through light microscopy following trypan blue and alizarin red staining. RESULTS: Overall mortality was 4.07%, 3.97% and 7.66%, in groups A, B and C, respectively, with percentages of uncovered areas of 0.31%, 1.36% and 0.20% (all p > 0.05). Endothelial cell density variation was 5.51%, 3.06% and 2.82% in groups A, B and C, respectively (p = 0.19). Total Endothelial Cell Loss (ECL) was 4.37%, 5.32% and 7.84% in groups A, B and C, respectively (p = 0.39). Endothelial cell morphology was comparable in all three groups. CONCLUSIONS: In the DMEK RAPID Mini, low temperatures (<2 °C) may affect the quality of pre-loaded grafts, inducing a higher ECL after 72 h of preservation, although no significant differences among groups could be proved. Our data would suggest maintaining grafts loaded in the DMEK RAPID Mini at temperatures between 2-8 °C for appropriate preservation.

Retromode Imaging Technology for Detecting Drusen-Like Deposits in Healthy Adults.

PURPOSE: To investigate the ability of retromode imaging technology to visualize drusen-like deposits (DLDs) in the macular region of healthy individuals without retinal diseases. Additionally, the correlation between subject age and the density of DLDs was assessed and their topographic distribution was evaluated. DESIGN: Prospective, observational, cross-sectional study SUBJECTS: Healthy volunteers (aged ≥ 35 years) without macular diseases. METHODS: This study evaluated macular images in healthy adults using color fundus photography (FP) and retromode imaging. Two masked graders counted the number of DLDs identifiable with each modality. The standardized ETDRS concentric rings were adopted to divide DLDs based on their topographic distribution. MAIN OUTCOME MEASURES: Comparison of the number of DLDs detected with each imaging modality. The association between DLDs and age. The topographic distribution of macular DLDs with retromode imaging. RESULTS: The study included 91 eyes of 52 healthy volunteers (mean ± standard deviation age, 57.9 ± 10.9 years; range, 36-82 years). Overall, at least 1 DLD was present in 63.74% of eyes on color FP and 96.71% on retromode. Retromode imaging allowed detection of significantly more DLDs compared with color FP within the ETDRS grid (median [interquartile range], 4 [1-14] vs. 0 [0-0] respectively; P < 0.001). The density of DLDs was higher in the outer and inner rings compared with the central subfield (relative risk [RR], 16.70; 95% confidence interval [CI], 10.3-27.3 vs. RR 17.1; 95% CI, 10.5-27.6, respectively). Age was significantly correlated with DLDs density in all 3 sectors (all P < 0.05). CONCLUSIONS: Retromode technology allowed the detection of a significantly higher number of DLDs compared with FP in the macula of healthy individuals. This noninvasive imaging modality could be used to investigate the effect of the aging process on the macula, fostering a better understanding of the pathophysiology of age-related macular diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intraoperative OCT for Lamellar Corneal Surgery: A User Guide.

Intraoperative OCT is an innovative and promising technology which allows anterior and posterior segment ocular surgeons to obtain a near-histologic cross-sectional and tomographic image of the tissues. Intraoperative OCT has several applications in ocular surgery which are particularly interesting in the context of corneal transplantation. Indeed, iOCT images provide a direct and meticulous visualization of the anatomy, which could guide surgical decisions. In particular, during both big-bubble and manual DALK, the visualization of the relationship between the corneal layers and instruments allows the surgeon to obtain a more desirable depth of the trephination, thus achieving more type 1 bubbles, better regularity of the plane, and a reduced risk of DM perforation. During EK procedures, iOCT supplies information about proper descemetorhexis, graft orientation, and interface quality in order to optimize the postoperative adhesion and reduce the need for re-bubbling. Finally, mushroom PK, a challenging technique for many surgeons, can be aided through the use of iOCT since it guides the correct apposition of the lamellae and their centration. The technology of iOCT is still evolving: a larger field of view could allow for the visualization of all surgical fields, and automated tracking and iOCT autofocusing guarantee the continued centration of the image.

Deep Learning Using Preoperative AS-OCT Predicts Graft Detachment in DMEK.

Purpose: To evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre-Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images. Methods: Retrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist. Results: In total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95% confidence interval) were as follows: F1 score, 0.77 (0.57-0.91); precision, 0.67 (0.44-0.88); specificity, 0.45 (0.15-0.75); sensitivity, 0.92 (0.73-1.00); and AUC, 0.63 (0.52-0.86). MIL-AI performance was more sensitive (92% vs. 31%) but less specific (45% vs. 64%) than the ophthalmologist's performance. Conclusions: The MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model. Translational Relevance: MIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.

Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, multicenter, cohort study. METHODS: We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal. RESULTS: The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P = .008), higher number of injections (P = .01), and worse baseline visual acuity (VA) (P = .03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001). CONCLUSIONS: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens.

Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol.

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.

Focal electroretinogram and microperimetry testing of photoreceptor-retinal pigment epithelium function in intermediate age-related macular degeneration.

PURPOSE: To compare the performance of focal electroretinogram (FERG) and fast mesopic microperimetry in evaluating macular function of intermediate age-related macular degeneration (iAMD) subjects with preserved visual acuity. METHODS: Cross-sectional, observational study. Participants with drusen >125 µm and VA ≥80 ETDRS letters and age- and sex-comparable healthy subjects were consecutively enrolled in the study. Three photopic FERG recordings of the central 9° of the macula with luminance modulated stimuli flickering at 42.5 Hz and a fast mesopic microperimetry with a custom pattern of 3 central (CS) and 3 paracentral (pCS) stimuli at 1.2° and 6° from fixation were acquired. RESULTS: Overall, 112 eyes of 77 participants (age 73.0 ± 7.1 years, 47 iAMD eyes) were analysed. Mean FERG amplitude, CS and pCS (all p < 0.05) were lower in the iAMD group. A significant association was observed between FERG amplitude and iAMD (OR 9.58, p < 0.001) in multiple logistic regression analysis. Z-scores of FERG were lower than microperimetry in iAMD (p = 0.002) but not for healthy participants. AUC of the ROC curve was greater for FERG than microperimetry (0.895 versus 0.644 and 0.675, both p < 0.05). CONCLUSION: Focal ERG objectively measures a cumulative response originating from the photoreceptor-RPE complex of the central 9° of the macula and demonstrated high accuracy in identifying decreased central macular function in iAMD patients with preserved visual acuity, performing better than fast mesopic microperimetry. Focal ERG should be considered a reliable technique for measuring retinal sensitivity of iAMD patients.