Retinal Pigment Epithelium Atrophy Research Articles

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium

Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative disease that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression. However, mechanisms by which molecular alterations of normal aging impair RPE function and contribute to AMD pathogenesis are unclear.Here, we specifically interrogate the RPE translatome with advanced age and across sexes in a novel RPE reporter mouse model. We find differential age- and sex- associated transcript expression with overrepresentation of pathways related to inflammation in the RPE. Concordant with impaired RPE function, the phenotypic changes in the aged translatome suggest that aged RPE becomes immunologically active, in both males and females, with some sex-specific signatures, which supports the need for sex representation for in vivo studies.

Leaking beehive honey sign an unusual case of central serous chorioretinopathy

Central serous chorioretinopathy is the fourth most common retinopathy after age-related macular degeneration, diabetic retinopathy and branch retinal vein occlusion. It’s usually unilateral and affect young or middle-aged men with M: F - 3:1 whereas female tend to be older. It’s a common ocular disease characterized by decompensation of the retinal pigment epithelium, which results in neurosensory retinal detachment, serous pigment epithelium detachment, and retinal pigment epithelium atrophy. Early identification and treatment are needed to prevent complications. Conclusion: Patients may require early intervention to prevent loss of photoreceptor layer integrity. Though Majority of cases are self-resolving, mineralocorticoid antagonists can be given for faster resorption of subretinal fluid. Photo Dynamic Therapy may be required for cases of chronic Central Serous Chorioretinopathy.

Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD.

Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD. Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss. The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA.

Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers.

The imagistic evaluation of non-neovascular age-related macular degeneration (AMD) is crucial for diagnosis, monitoring progression, and guiding management of the disease. Dry AMD, characterized primarily by the presence of drusen and retinal pigment epithelium atrophy, requires detailed visualization of the retinal structure to assess its severity and progression. Several imaging modalities are pivotal in the evaluation of non-neovascular AMD, including optical coherence tomography, fundus autofluorescence, or color fundus photography. In the context of emerging therapies for geographic atrophy, like pegcetacoplan, it is critical to establish the baseline status of the disease, monitor the development and expansion of geographic atrophy, and to evaluate the retina's response to potential treatments in clinical trials. The present review, while initially providing a comprehensive description of the pathophysiology involved in AMD, aims to offer an overview of the imaging modalities employed in the evaluation of non-neovascular AMD. Special emphasis is placed on the assessment of progression biomarkers as discerned through optical coherence tomography. As the landscape of AMD treatment continues to evolve, advanced imaging techniques will remain at the forefront, enabling clinicians to offer the most effective and tailored treatments to their patients.

Choroidal osteoma secondary to chronic posterior scleritis: A case report and literature review

Choroidal osteoma is a rare benign ossifying tumor of the choroid. Posterior scleritis is an uncommon yet potentially sight-threatening inflammation of the sclera. Herein, we report a case of choroidal osteoma secondary to chronic posterior scleritis accompanied by a literature review. Decalcification of the tumor, choroidal neovascularization, and retinal pigment epithelium atrophy can result in blindness. Hence, patients with recurrent posterior scleritis need long-term follow-up; in addition, we need to be alert for complications, such as choroidal osteoma, which can ultimately lead to a poor visual prognosis.

Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate

Investigate associations between geographic atrophy (GA) growth rate and multimodal imaging biomarkers and patient demographics in patients with advanced non-neovascular age-related macular degeneration (nnAMD). Prospective cohort study. One hundred twenty-one eyes of 66 patients with advanced nnAMD with GA enrolled in the University of Colorado AMD Registry from August 2014 to June 2021, with follow-up through June 2023. Multimodal images were reviewed by two graders for imaging biomarkers at enrollment. GA growth rate and square-root transformed (SQRT) GA growth rate were measured between enrollment and final visit. Associations between the outcome SQRT GA growth rate and imaging biomarkers, baseline GA lesions characteristics, and patient demographics were evaluated. Average GA growth rate was 1.430 mm2/year and SQRT GA growth rate was 0.268 mm/year over a mean of 3.7 years. SQRT GA growth rate was positively associated with patient age (P = .010) and female sex (0.035), and negatively associated with body mass index (0.041). After adjustment for these demographic factors, SQRT GA growth rate was positively associated with presence of non-exudative subretinal fluid (P < .001), non-exudative subretinal hyperreflective material (P = .037), and incomplete retinal pigment epithelium and outer retina atrophy (P = .022), and negatively associated with subfoveal choroidal thickness (P = .031) and presence of retinal pseudocysts (P = .030). Larger baseline GA size at enrollment was associated with faster GA growth rate (P = .002) but not SQRT GA growth rate. Select patient demographic factors and basic clinically-relevant imaging biomarkers were associated with GA growth rate. These biomarkers may guide patient selection when considering treating GA patients with novel therapeutics.

Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).

The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes. This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations. Mean patient age was 80.5 ± 6.2 years. The mean length of total follow-up was 39.7 ± 13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8 ± 355.5 µm from the first consultation to 562.8 ± 251.5 µm at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p = 0.004, n = 14). The mean visual acuity before rupture was 66.2 ± 16.0 letters. Mean visual acuity deteriorated to 60.8 ± 18.6 letters at the first consultation after rupture (p = 0.052, n = 21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5 ± 23.7 ETDRS letters (p = 0.23, n = 19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35 ± 2.94 mm2 (baseline) to 6.81 ± 6.25 mm2 over the course of 2 years (p = 0.000 013, n = 20). The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.

Complete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: A Longitudinal Evaluation.

There is a need for robust earlier biomarkers of atrophic age-related macular degeneration (AMD) that could act as surrogate endpoints for the geographic atrophy (GA) in early interventional trials. This study sought to examine the risk of progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) to the traditional atrophic endpoint of GA on color fundus photography (CFP). This study also compared the risk of progression for cRORA to that associated with the specific OCT features that define nascent GA (nGA), a strong predictor for GA development. One-hundred and forty participants with bilateral large drusen at baseline underwent OCT imaging and CFP at 6-monthly intervals for up to 36 months. OCT volume scans were graded for the presence of cRORA and nGA, and CFPs were graded for the presence of GA. The association and rate of progression to GA for cRORA and nGA were examined. Both cRORA and nGA were significantly associated with GA development (adjusted hazard ratio [HR], 65.7 and 76.8 respectively; both P<0.001). The probability of progression of cRORA to GA over 24-months (26%) was significantly lower than the probability for progression of nGA (38%; P=0.039). This study confirmed that cRORA was a significant risk factor for developing GA, although its rate of progression was slightly lower compared to nGA. Whilst requiring replication in future studies, these findings suggest that the specific features of photoreceptor degeneration used to define nGA appear important when assessing risk of progression.

Dose-Dependent Progression of Chorioretinal Atrophy at the Injection Site After Subretinal Injection of rAAV2/8 in Nonhuman Primates

ObjectiveProgressive retinal atrophy has been described after subretinal gene therapy utilizing the adeno-associated virus (AAV) vector platform. To elucidate whether thIS atrophy is a consequence of inherent properties of AAV, or if it is related to the surgical trauma of subretinal delivery, we analyzed data from an IND-enabling study for PDE6A gene therapy in non-human primates. DesignAnimal study (non-human primates), retrospective data analysis SubjectsForty eyes of thirty healthy non-human primates (macaca fascicularis) were included in the analysis. Two AAV dose levels (low: 1x10E11, high: 1x10E12) were compared to sham-injection (balanced saline solution; BSS). Twenty untreated eyes were not analysed. MethodsAnimals were treated with a sutureless 23G vitrectomy and single subretinal injections of AAV.PDE6A and/or BSS. The follow up period was 12 weeks. Atrophy development was followed using fundus-autofluorescence (AF), optical coherence tomography (OCT), fluorescence angiography (FA) and indocyanine green angiography (ICGA). Main Outcome MeasuresArea [mm2] of retinal pigment epithelium (RPE) atrophy on AF. Presence of outer retinal atrophy on OCT. Area [mm2] of hyperfluorescence in FA and hypofluorescence in ICGA. ResultsProgressive atrophy at the injection site developed in 54% of high dose, 27% of low dose, and 0% of sham-treated eyes. At the end of observation, the mean±SD area of atrophy in AF was 1.19±1.75 mm2, 0.25±0.50 mm2 and 0.0±0.0 mm2 respectively (sham x high dose: p=0.01). Atrophic lesions in AF (p=0.01) and FA (p=0.02) were significantly larger in high dose eyes, compared to sham-treated eyes. Rate of progression in high dose eyes was 4.1x higher compared to low dose eyes. ConclusionSubretinal injection of AAV.PDE6A induced dose-dependent, progressive retinal atrophy at the site of injection. Findings from multimodal imaging were in line with focal, transient inflammation within the retina and choroid and secondary atrophy. Atrophic changes after gene therapy with AAV-based vector systems are not primarily due to surgical trauma and increase with the dose given.

Suspected Retinal Toxicity After Multiple Intravitreal Ganciclovir Injections in a Patient of CMV Retinitis

ABSTRACT Purpose Intravitreal Ganciclovir has been one of the treatments of choice for cytomegalovirus (CMV) retinitis and has been used extensively for its treatment since 1987. It has not been shown to have any major adverse effects. There are no reports on any retinal toxicity even after multiple, repeated injections. Herein, we report a rare case of retinal toxicity after multiple intravitreal injections in a patient of CMV retinitis. Case Report A 69-year-old one eyed male, who was on oral corticosteroids and systemic immunosuppression for Granulomatosis with Polyangiitis, presented with CMV retinitis in both eyes. His visual acuity was 20/60 in his right eye and no perception of light in his left eye. He was treated with multiple injections of intravitreal Ganciclovir in his right eye. The left eye was not treated since it had no vision potential. The right eye of the patient which had received multiple injections went on to developed a progressive diffuse atrophy of Retinal Pigment Epithelium (RPE). No such changes were noted in the left eye of the patient. Conclusion and Importance We present a case of progressive diffuse RPE atrophy as a result of toxicity of intravitreal ganciclovir injections. It is important to be aware of this rare potential toxicity of intravitreal Ganciclovir.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. Mean age was 75.17 ± 2.51years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32foci/mm2 in the SDD group versus 13,253 ± 3331.00foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

Morphological Biomarkers Related to Visual Acuity in Patients With Radiation Retinopathy Treated With Intravitreal Ranibizumab.

Our objective was to monitor variables via spectral-domain optical coherence tomography (SD-OCT) and identify the most relevant biomarkers related to best-corrected visual acuity (BCVA) in radiation retinopathy (RR). A post-hoc analysis of the two-year Ranibizumab for Radiation Retinopathy (RRR) trial analyzed vision and OCT parameters including intraretinal fluid, ellipsoid zone (EZ) disruption, retinal pigment epithelium atrophy, hard exudates, retinal hemorrhage, retinal neovascularization, and subfoveal fluid. BCVA and SD-OCT parameters were evaluated by univariate analysis and a mixed-effects model. Forty eyes from the RRR trial were included. Intraretinal cyst vertical size (week 24: P = 0.032; week 48: P = 0.021), neovascularization (week 48: P = 0.028; week 72: P = 0.025), and EZ disruption (week 72: P = 0.029; week 104: P = 0.019) were the clinical parameters most relevant to BCVA by univariate analysis in at least two time points. The mixed-effects model confirmed the relevance of intraretinal cyst vertical size (P = 0.001) and neovascularization (P = 0.001) but not EZ disruption (P = 0.119) over the course of the study. This study characterizes the course of visual loss in RR by identifying intraretinal cyst vertical size, neovascularization, and EZ disruption as biomarkers of poor BCVA over a span of two years. Larger multicenter studies are needed to confirm these findings. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Topographic analysis of local OCT biomarkers which predict progression to atrophy in age-related macular degeneration.

To define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that location in eyes with age-related macular degeneration (AMD). In this retrospective case-control study, patients with dry AMD who had evidence of cRORA and OCT data available for 4years (48 ± 4months) prior to the first visit with evidence of cRORA were included. The visit 4years prior to the development of cRORA was defined as the baseline visit, and the region on the OCT B-scans of future cRORA development was termed the case region. A region in the same eye at the same distance from the foveal center as the case region that did not progress to cRORA was selected as the control region. OCT B-scans at the baseline visit through both the case and control regions were evaluated for the presence of soft and cuticular drusen, drusen with hyporeflective cores (hcD), drusenoid pigment epithelial detachments (PED), subretinal drusenoid deposits (SDD), thick and thin double-layer signs (DLS), intraretinal hyperreflective foci (IHRF), and acquired vitelliform lesions (AVL). A total of 57 eyes of 41 patients with dry AMD and evidence of cRORA were included. Mean time from the baseline visit to the first visit with cRORA was 44.7 ± 6.5months. The presence of soft drusen, drusenoid PED, AVL, thin DLS, and IHRF at the baseline visit was all associated with a significantly increased risk of cRORA at that location. Multivariable logistic regression revealed that IHRF (OR, 8.559; p < 0.001), drusenoid PED (OR, 7.148; p = 0.001), and a thin DLS (OR, 3.483; p = 0.021) were independent predictors of development of cRORA at that location. IHRF, drusenoid PED, and thin DLS are all local risk factors for the development of cRORA at that same location. These findings would support the inclusion of these features within a more granular staging system defining specific steps in the progression from early AMD to atrophy.

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3-dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.

Multimodal Retinal Imaging Reveals New Pathogenic Insights in Central Areolar Choroidal Dystrophy: A Case Series.

To describe novel imaging findings in a family affected by central areolar choroidal dystrophy (CACD). Case series with multimodal retinal imaging assessment. A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium (RPE). Blue-light autofluorescence (BAF) of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence (NIR-AF). Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyper-autofluorescent using BAF and as hypo-autofluorescent using NIR-AF. Optical coherence tomography angiography (OCT-A) revealed several tiny areas of flow voids in correspondence of the RPE alterations of both eyes.Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of RPE atrophy surrounded by yellowish deposits and a hypo-pigmented halo.Next-generation genetic analysis for inherited macular dystrophies was performed on the index case and the affected family members and revealed a p.Arg172Gln missense mutation in PRPH2 gene, leading to the diagnosis of CACD. Multimodal imaging can reveal new pathogenic insights in CACD. Of notice, NIR-AF and OCT-A are able to detect RPE hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.

Morphometric Risk Factors for Drusenoid Pigment Epithelium Detachment Collapse and Retinal Pigment Epithelium Atrophy Expansion.

The purpose of this study was to investigate factors associated with drusenoid pigment epithelium detachment (dPED) growth rate, incidence of dPED collapse, and retinal pigment epithelium (RPE) atrophy enlargement rate following dPED collapse and their impact on visual acuity (VA). This was a retrospective longitudinal study on 44 eyes. Serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF) imaging were performed. Qualitative features and quantitative dPED-related metrics were assessed. The surface-to-volume ratio (S/V) was computed to evaluate dPED shape irregularity. AF imaging was utilized to measure RPE atrophy area in eyes experiencing dPED collapse. Regression models were used to analyze associations among VA, dPED growth rate, and RPE atrophy enlargement rate. Cox regression was used to identify risk factors for dPED collapse. Significant correlations were observed between dPED area, surface, and volume (P < 0.05 for all pairs). The dPED metrics were inversely correlated with the S/V. Incidence of dPED collapse was 22 per 100 eye-years over a mean follow-up of 59 ± 41 months. Eyes experiencing collapsed dPED had worse baseline VA (P < 0.001). RPE hypertransmission (hazard ratio [HR] = 3.68, P = 0.004) and hyper-reflective foci (HR = 3.45, P = 0.02) were risk factors for dPED collapse; a higher S/V ratio was protective (HR = 0.78, P = 0.03). A faster rate of RPE atrophy enlargement was associated with a faster rate of dPED volume increase (r = 0.47, P = 0.02) and worse VA over time (P = 0.02). Risk stratification in patients with dPED can be aided by identifying risk factors for dPED collapse. Identifying factors associated with RPE atrophy enlargement may have implications for treatment decision making.

CHOROIDAL NEOVASCULARIZATION IN A CHILD WITH DOWN SYNDROME

Purpose: To report a case of Down syndrome with myopic choroidal neovascularization (CNV) and the treatment outcome. Methods: Case report. Main outcome measures include refractive error, fundus examination, optical coherence tomography (OCT), OCT angiography (OCTA), fluorescein angiography (FA), anti-vascular endothelial growth factor (VEGF) injections. Results: A 12-year-old boy with Down syndrome presented at a regular check-up with decreased visual acuity (VA) with macular degeneration in the left eye. The best-corrected VA was 0.6 in the right eye and 0.1 in the left eye, which decreased from 0.3 1 year ago. The refractive error (spherical equivalent) was -5.25 diopters (D) in the right eye and -8.00 D in the left eye. Detailed examinations were performed under general anesthesia. The fundus examination showed macular degeneration with retinal pigment epithelium (RPE) atrophy, pigmentary changes, and fibrous tissue in the left eye. OCT showed CNV at the macula with edema, and OCTA showed spreading CNV above the RPE at the macula in the left eye. FA showed hyperfluorescence in the early phase and late dye leakage from the CNV. Intravitreal ranibizumab injections were administered twice within 2 months, and he maintained a VA of 0.1 in the left eye. Conclusion: CNV and associated macular degeneration may occur in Down syndrome with high myopia possibly because of the abnormal choroidal structure. In children with Down syndrome, regular fundus examinations with OCT are important for early detection and treatment of CNV.

Acute atrophic evolution of drusenoid pigment epithelium detachment after photobiomodulation

Purpose: To report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration (AMD). Methods: Optical coherence tomography (OCT) was performed in the study eye before and after PBM. Results: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM the D-PED collapsed, resulting in incomplete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening. Conclusion: Thinning of the outer retinal layers over a D-PED and posterior hypertrasmission may represent bad prognostic factors for PBM, accelerating the lesion’s natural history towards atrophic evolution.