Long-term follow-up demonstrates change in conformation shape of the focal choroidal excavation lesions.

PURPOSE: This study aims to present long-term observation of 5 eyes with focal choroidal excavation (FCE), focusing on morphological changes in conformity of the lesion. METHODS: A retrospective case series was conducted, including 5 eyes of 5 patients with FCE. The study utilized multimodal imaging including color fundus photography, optical coherence tomography (OCT), enhanced depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), red free imaging, and OCT angiography. RESULTS: The mean age at diagnosis was 51 ± 10.65 years, with a mean follow-up period 37 ± 13.59 months. All cases were unilateral, with 1 presenting FCE as an isolated lesion, and one patient exhibiting 2 FCEs in one eye. The mean choroidal thickness measured by EDI-OCT was 268.2 ± 63.39 µm in the affected eye. One patient displayed choroidal thickening and pachyvessels. Of the 5 eyes, one had conforming and 4 non-conforming FCE. We observed a conversion in conformity in all patients, with 4 cases transitioning from non-conforming FCE to conforming type (3 spontaneously, 1 treatment-induced). In conforming FCE, a hyporeflective space appeared twice between neuroretina and retinal pigment epithelium with spontaneous regression. CONCLUSION: We observed change in shape from the conforming to non-conforming FCE and vice versa in all patients. We consider this small change in the hyporeflective space as non-pathologic and clinically insignificant.

Chorioretinal Atrophy Growth After Voretigene Neparvovec Retinotopically Is Connected to Retinal Functional Rescue.

Purpose: Chorioretinal atrophy growth after voretigene neparvovec has been reported recently with its positive correlation with successful treatment. This finding raised the question on long-term effects and the etiology of the chorioretinal atrophy. Methods: Using local retinal functional diagnostics, we tested whether the atrophy growth is connected to the initial local functional improvement after the therapy. Results: The results describe factors predicting the development of atrophy. First, the atrophy emerges after approximately 3 months in an area with local functional rescue before. The areas of the greatest gain in the number of functionally rescued rods are prone to be the initial spots of atrophy growth in almost one-half of the cases and the retinotopy corresponds with the area of a high number of post-treatment functioning rods. Second, the dark-adapted perimetry shows that the atrophy growth is in the area with functioning rescued rods. However, the rods with the greatest sensitivity gain are not the parts of the growing atrophy in the first 2 years after intervention. This preservation of rods with the greatest sensitivity seems to explain the excellent profile of rods rescue over the long term measured by full-field stimulus threshold and reported earlier. Conclusions: A disbalance between the increase of functional rods and their threshold shortly after treatment could be an indicator for a metabolic origin of chorioretinal atrophy after voretigene neparvovec. Translational Relevance: A basic understanding of the photoreceptor rescue aspects after gene therapy can demonstrate a metabolic causal influence of the efficacy on the development of side effects, such as chorioretinal atrophy.

Choroid cavitation associated with macular coloboma. Multimodal study. Image en face.

Intrachoroidal cavitation is a finding identified with OCT initially described in myopic patients, it also appears in non-myopic patients. It can occur in both the peripapillary area and the posterior pole. Macular coloboma is a defect of embryonic development of the posterior pole, in structural OCT the absence of the retinal pigment epithelium and choroidal vessels is essential. In this case, intrachoroidal cavitation circumscribes the macular coloboma, in the absence of an intercalary membrane. The en face image allows us to assess the relationship between the two structures as well as their magnitude.

Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study.

Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable retinal cells. PERCEIVE is an ongoing, post-authorization, prospective, multicenter, registry-based observational study and is the largest study assessing the real-world, long-term safety and effectiveness of VN. Here, we present the outcomes of 103 patients treated with VN according to local prescribing information. The mean (SD) age was 19.5 (10.85) years, 52 (50.5%) were female, and the mean (SD) duration of the follow up was 0.8 (0.64) years (maximum: 2.3 years). Thirty-five patients (34%) experienced ocular treatment-emergent adverse events (TEAEs), most frequently related to chorioretinal atrophy (n = 13 [12.6%]). Eighteen patients (17.5%; 24 eyes [13.1%]) experienced ocular TEAEs of special interest, including intraocular inflammation and/or infection related to the procedure (n = 7). The mean (SD) changes from baseline in full-field light-sensitivity threshold testing (white light) at month 1, month 6, year 1, and year 2 were -16.59 (13.48) dB (51 eyes), -18.24 (14.62) dB (42 eyes), -15.84 (14.10) dB (10 eyes), and -13.67 (22.62) dB (13 eyes), respectively. The change in visual acuity from baseline was not clinically significant. Overall, the outcomes of the PERCEIVE study are consistent with the findings of VN pivotal clinical trials.

Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches.

Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females. Clinically, it manifests as small, yellowish-white lesions in the inner choroid and outer retina, often associated with inflammatory changes. Accurate diagnosis remains a challenge due to its resemblance to other posterior uveitic entities, necessitating an astute clinical eye and advanced imaging techniques for differentiation. Multimodal imaging plays a crucial role by offering valuable insights, as it enables the visualization of various abnormalities related to uveitis. The pathogenesis of PIC is still a subject of debate, with a complex interplay of genetic, immunological, and environmental factors proposed. Managing PIC presents multiple challenges for clinicians. Firstly, variable disease severity within and among patients requires diverse treatments, from observation to aggressive immunosuppression and/or anti-VEGF therapy. Secondly, treatment must distinguish between primary causes of vision loss. New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes. Thirdly, deciding on maintenance therapy is complex, balancing PIC prognosis variability against immunosuppression risks. Some patients have long periods of inactivity and remission, while others face sudden, vision-threatening episodes during quiescent phases. Through a systematic review of the literature, this paper sheds light on the current understanding of PIC, its challenges, and the prospects for future research. By synthesizing existing knowledge, it aims to aid clinicians in accurate diagnosis and guide treatment decisions for improved visual outcomes in individuals affected by PIC.

A proposal for an updated staging system for LCHADD retinopathy.

OBJECTIVE: To develop an updated staging system for long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHADD) chorioretinopathy based on contemporary multimodal imaging and electrophysiology. METHODS: We evaluated forty cases of patients with genetically confirmed LCHADD or trifunctional protein deficiency (TFPD) enrolled in a prospective natural history study. Wide-field fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinogram (ffERG) were reviewed and graded for severity. RESULTS: Two independent experts first graded fundus photos and electrophysiology to classify the stage of chorioretinopathy based upon an existing published system. With newer imaging modalities and improved electrophysiology, many patients did not fit cleanly into a single traditional staging group. Therefore, we developed a novel staging system that better delineated the progression of LCHADD retinopathy. We maintained the four previous delineated stages but created substages A and B in stages 2 to 3 to achieve better differentiation. DISCUSSION: Previous staging systems of LCHADD chorioretinopathy relied on only on the assessment of standard 30 to 45-degree fundus photographs, visual acuity, fluorescein angiography (FA), and ffERG. Advances in recordings of ffERG and multimodal imaging with wider fields of view, allow better assessment of retinal changes. Following these advanced assessments, seven patients did not fit neatly into the original classification system and were therefore recategorized under the new proposed system. CONCLUSION: The new proposed staging system improves the classification of LCHADD chorioretinopathy, with the potential to lead to a deeper understanding of the disease's progression and serve as a more reliable reference point for future therapeutic research.

Unilateral solitary choroidal tuberculoma as the presenting sign in disseminated tuberculosis in an immunocompetent patient.

INTRODUCTION: Tuberculosis can involve any organ in the body including ocular tissue of which the uveal tissue is most commonly infected. Choroidal involvement ranges from choroidal tubercles to granulomas. This is one of the few cases of a solitary choroidal granuloma with no other systemic symptoms in an immunocompetent child. METHOD: A case report. RESULTS: A 12-year-old female, presented with diminution of vision in the left eye for a month. The anterior segment of her left eye was normal. A fundus examination revealed an isolated orangish-yellow choroidal mass, 4 DD in size, involving the posterior pole with overlying subretinal exudation. CT scan of the thorax showed large pulmonary, cervical and pancreatic lymph nodes, along with lytic lesions of the thoracic vertebrae. Excision biopsy of the cervical lymph nodes showed caseating granulomas with no e/o malignancies on histopathology. The patient was started on anti-tubercular therapy. Six months after the treatment, the lesion had reduced in size and her vision had improved. CONCLUSION: Isolated choroidal tuberculomas can be present in eyes with little associated ocular inflammation and no other symptoms of systemic tuberculosis. High suspicion, early diagnosis and rapid initiation of medication are important for the treatment of ocular and systemic tuberculosis.

Long-term sequelae of photic eye injury from a solar eclipse.

Photic ocular injuries are secondary traumatic injuries resulting from the toxic effects of the interaction between light and the eye, particularly the retina. We report the cases of two patients who experienced photic macular injury from their early childhood due to observing a solar eclipse without protection. The retinal lesions are mainly macular; these can be serious and irreversible. They are the consequence of photochemical, photomechanical and photothermal reactions. OCT is very useful for the diagnosis of these foveal lesions. The visual prognosis of solar retinopathy is generally favorable. However, some patients may develop permanent sequelae with a decrease in visual acuity. Management remains empirical and controversial. Thus, prevention and public education remain the only effective ways to avoid this type of trauma.

Classification and Growth Rate of Chorioretinal Atrophy after Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Degeneration.

PURPOSE: Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration. DESIGN: Multicenter retrospective analysis. SUBJECTS: Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy. METHODS: Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with ≥ 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area. MAIN OUTCOME MEASURES: Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models. RESULTS: Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated > 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3 mm2/year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm2/year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm2/year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P < 0.05). CONCLUSIONS: Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

POLYPOIDAL LESIONS ASSOCIATED WITH CHOROIDAL NEVI.

PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.

RISK OF EXUDATION IN EYES WITH NONEXUDATIVE POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate the characteristics and natural history of treatment-naive nonexudative polypoidal choroidal vasculopathy (PCV) and to determine biomarkers predicting exudative conversion. METHODS: Patients diagnosed with nonexudative PCV based on indocyanine green angiography and optical coherence tomography were included. Incidence of exudative conversion in nonexudative PCV patients and cumulative estimates for overall risk were assessed. Indocyanine green angiography and optical coherence tomography imaging-based features were analyzed to identify risk factors for exudative conversion. RESULTS: The study included 42 eyes of 40 patients with nonexudative PCV. The mean follow-up duration was 54.3 ± 35.5 months. Of the 42 eyes with nonexudative PCV, exudative conversion developed in 23 eyes (54.8%) after 42.2 ± 28.3 months (range, 8-103 months). Kaplan-Meier analysis showed that the exudation-free survival at 5 years after baseline was estimated to be 53.6%. Multivariate regression analysis showed that sequentially increased protrusion of retinal pigment epithelium in the polyp area was a significant risk factor for exudation in nonexudative PCV (odds ratio = 10.16; 95% CI 1.78-57.81; P = 0.01). CONCLUSION: Exudative conversion has been noted in nearly half of the nonexudative PCV cases in 5 years. The progressive protrusion of polypoidal lesions on optical coherence tomography examination may be a significant biomarker for predicting the near-term onset of exudation.

MULTIMODAL RETINAL IMAGING REVEALS NEW PATHOGENIC INSIGHTS IN CENTRAL AREOLAR CHOROIDAL DYSTROPHY: A CASE SERIES.

PURPOSE: To describe novel imaging findings in a family affected by central areolar choroidal dystrophy. METHODS: Case series with multimodal retinal imaging assessment. RESULTS: A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium. Blue-light autofluorescence of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence. Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyperautofluorescent using blue-light autofluorescence and as hypoautofluorescent using near-infrared autofluorescence. Optical coherence tomography angiography revealed several tiny areas of flow voids in correspondence of the retinal pigment epithelium alterations of both eyes. Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of retinal pigment epithelium atrophy surrounded by yellowish deposits and a hypopigmented 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 central areolar choroidal dystrophy. CONCLUSION: Multimodal imaging can reveal new pathogenic insights in central areolar choroidal dystrophy. Of notice, near-infrared autofluorescence and optical coherence tomography angiography are able to detect retinal pigment epithelium hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.

CLINICAL CHARACTERISTICS, TREATMENT MODALITIES, AND THEIR ASSOCIATION WITH LONG-TERM VISUAL OUTCOMES IN UVEAL EFFUSION SYNDROME.

PURPOSE: Uveal effusion syndrome (UES) is a rare eye condition characterized by fluid accumulation in the uveal layer. We investigated its clinical characteristics and treatment modalities and their association with long-term visual outcomes. METHODS: This retrospective cohort study included patients with UES treated at two tertiary hospitals between November 2005 and June 2023. Clinical characteristics and treatment outcomes by modality were compared between nanophthalmic Type 1 UES (UES-1) and non-nanophthalmic Type 2 UES (UES-2), and between initial and final visits. Logistic regression analysis was used to identify factors associated with vision loss. RESULTS: Twenty-three eyes were included (UES-1, n = 10; UES-2, n = 13). Retinal pigment epithelium mottling was significantly more common in UES-1 than in UES-2 ( P = 0.043); no other between-group differences were observed. Post-treatment, in UES-1, best-corrected visual acuity ( P = 0.028) and central macular thickness ( P = 0.046) significantly decreased; in UES-2, best-corrected visual acuity significantly improved ( P = 0.021), and subfoveal choroidal thickness ( P = 0.048), central subretinal fluid height ( P = 0.011), and central macular thickness ( P = 0.010) significantly decreased. UES-2 was associated with a lower risk of vision loss (odds ratio, 0.024; P = 0.044). No other associated factors were identified. CONCLUSION: The UES type was the sole independent prognostic factor for vision loss, whereas treatment modalities had no significant impact on visual outcomes.

Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression.

PURPOSE: To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. METHODS: This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. RESULTS: BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). CONCLUSIONS: Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.