Voretigene neparvovec for inherited retinal dystrophy due to RPE65 mutations: a scoping review of eligibility and treatment challenges from clinical trials to real practice.

Biallelic mutations in the RPE65 gene affect nearly 8% of Leber Congenital Amaurosis and 2% of Retinitis Pigmentosa cases. Voretigene neparvovec (VN) is the first gene therapy approach approved for their treatment. To date, real life experience has demonstrated functional improvements following VN treatment, which are consistent with the clinical trials outcomes. However, there is currently no consensus on the characteristics for eligibility for VN treatment. We reviewed relevant literature to explore whether recommendations on patient eligibility can be extrapolated following VN marketing. We screened 166 papers through six research questions, following scoping reviews methodology, to investigate: (1) the clinical and genetic features considered in VN treatment eligibility; (2) the psychophysical tests and imaging modalities used in the pre-treatment and follow-up; (3) the potential correlations between visual function and retinal structure that can be used to define treatment impact on disease progression; (4) retinal degeneration; (5) the most advanced testing modalities; and (6) the impact of surgical procedure on treatment outcomes. Current gaps concerning patients' eligibility in clinical settings, such as pre-treatment characteristics and outcomes are not consistently reported across the studies. No upper limit of retinal degeneration can be defined as the univocal factor in patient eligibility, although evidence suggested that the potential for function rescue is related to the preservation of photoreceptors before treatment. In general, paediatric patients retain more viable cells, present a less severe disease stage and show the highest potential for improvements, making them the most suitable candidates for treatment.

A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice.

BACKGROUND: Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support. RESULTS: The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers' needs and expectations must be acknowledged and discussed. CONCLUSION: As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.

Optic nerve involvement in CACNA1F-related disease: observations from a multicentric case series.

BACKGROUND: Congenital Stationary Night Blindness (CSNB) constitutes a group of non-progressive retinal disorders characterized by disturbances in scotopic vision and/or by a delay in adaptation to darkness, as well as by low visual acuity, myopia, nystagmus, and strabismus. Color vision and fundus appearance tend to be normal. To date, several CACNA1F gene variants have been linked to a CSNB phenotype but only few reports have focused on the optic nerve in this disease. MATERIALS AND METHODS: Twelve patients underwent standard ophthalmological and genetic evaluation including spectral domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), kinetic perimetry, fundus photography, magnetic resonance imaging (MRI), and next-generation sequencing (NGS). Bilateral thinning of the peripapillary nerve fiber layer (pRNFL) and the ganglion cell complex (GCC) supported involvement of the optic nerves. MRI, when available, was assessed for gross intracranial optic pathway abnormalities. RESULTS: All patients were shown to carry pathogenic variants in the CACNA1F gene, and all showed signs of optic nerve involvement. All patients showed a certain degree of myopic refractive error. Low average pRNFL thickness was evident in all patients. In three of them, pRNFL thickness was evaluated longitudinally and was proven to be stable over time. MRI imaging was unremarkable in all cases. CONCLUSION: Our data support the hypothesis that CACNA1F could be related to early-onset or congenital optic nerve involvement without any signs of a progressive optic neuropathy. Even though additional data from larger cohorts and longer follow-up periods are needed to further support and confirm our findings, there is a clear significance to our findings in the preparation for future CACNA1F gene therapy trials.

Choroidal Caverns in Stargardt Disease.

Purpose: To report choroidal caverns in patients affected by recessive Stargardt disease (STGD1) and to investigate its clinical features. Methods: Retrospective analysis of STGD1 patients recruited at the Regional Reference Center for Hereditary Retinal Degenerations at the Eye Clinic in Florence from 2012 to 2017. Patients included in the study underwent a complete ophthalmic examination including best-corrected visual acuity, color fundus photography, fundus autofluorescence, optical coherence tomography (OCT) and OCT angiography. Results: Eighty-six patients (172 eyes) were included in the study. Twenty-three eyes (13.3%) of 21 patients presented choroidal caverns. The total number of detected choroidal caverns was 63. Choroidal caverns were only present in patients with stage III and IV STGD. Interestingly, patients with choroidal caverns presented larger macular atrophy (20.53 ± 16.9 mm2 vs. 18.11 ± 20.39 mm2), worse visual acuity (1.03 ± 0.29 vs. 0.83 ± 0.26), and a thinner choroidal thickness (245.9 ± 88.7 vs. 266.0 ± 110.5 µm). Conclusions: Choroidal caverns are present only in the advanced stage of STGD1, and a possible degenerative origin of the finding has been hypothesized.

A Case Report of Pseudoxanthoma Elasticum with Rare Sequence Variants in Genes Related to Inherited Retinal Diseases.

A case of a patient with an early and severe visual impairment is described. Due to the occurrence of skin papules a suspect of pseudoxanthoma elasticum (PXE) was posed. PXE is a rare autosomal recessive disease clinically characterized by skin, cardiovascular and ocular manifestations, these last being those that most severely affect patients' quality of life. A whole exome sequencing approach focusing on 340 genes related to the calcification process and/or to inherited retinal diseases (IRDs) was performed. Rare monoallelic sequence variants in ABCA4, ABCC6, IMPG1, POC1B and RAX2 were found. The presence of calcified elastic fibers was assessed by ultrastructural analysis on a skin biopsy. Diagnosis of PXE was based on clinical, biomolecular and morphological results, although the additional involvement of several IRD genes is important to explain the unexpectedly severe ophthalmological phenotype of the patient also in prognostic and therapeutic perspectives. Data indicate that genetic screening using a wide-spectrum analysis approach is essential to assist ophthalmologists in improving patient counseling.

Lamellar Hole-associated Epiretinal Proliferation in choroideremia: a case report.

BACKGROUND: To report a clinical case of a patient affected with choroideremia (CHM) who underwent macular surgery for a macular hole (MH) with Lamellar Hole-associated Epiretinal Proliferation (LHEP). CASE PRESENTATION: We have described a 48-year-old male patient affected with CHM who developed MH with LHEP over a 7-year follow-up. The patient was referred to the Regional Center for Hereditary Retinal Degenerations of the Eye Clinic in Florence (Italy) in April 2012. The patient underwent vitrectomy and Inner Limiting Membrane (ILM) and LHEP peeling with fluid-air exchange. Ultra-structural examination of the excised epiretinal proliferation, carried out using electron microscopy, showed dense amorphous material, mainly composed of abundant clusters of fibrous collagens resembling compact fibrous long spacing collagen (FLSC), embedded in native vitreous collagen (NVC) and type IV collagen. No cells were detected in any of the specimens collected. At the 3rd-week postoperative follow-up the macular hole was closed. CONCLUSION: Macular hole with LHEP can be detected in CHM patients; in our patient the macular hole showed tractional and degenerative features, with good anatomical results after macular surgery.

Outcome and genetic analysis of patients affected by retinal capillary hemangioblastoma in von Hippel Lindau syndrome.

Purpose: To describe genetic analysis, treatment results, and complications of patients affected by retinal capillary hemangioblastoma (RCH) in von Hippel Lindau (VHL) syndrome. Methods: We collected 17 patients with VHL syndrome, who underwent a molecular test and an ophthalmic evaluation at the Eye Clinic of the University Hospital of Florence from January 2005 to February 2020. We focused on eyes showing RCHs examined using color fundus photographs, fluorescein angiography, and optical coherence tomography. Results: Eight eyes of six patients (6/17; 35%) showed RCHs at the fundoscopic examination. All RCHs were treated with laser therapy. Three eyes underwent episcleral surgery, one eye showing vitreous hemorrhage received three intravitreal (IV) anti-VEGF injections and three cryotherapy procedures, and one eye underwent vitrectomy. In patients with RCHs, five were characterized by a truncating mutation of the VHL protein, and one patient showed a missense mutation. We have reported two VHL mutations not reported in literature. Conclusions: Patients with multiple RCHs, who developed RCH secondary effects, showed truncating mutations of the VHL protein. We recommend early screening and close monitoring, especially if RCHs are detected at presentation, for every patient with VHL syndrome independently of the results of the molecular test for a missense or a truncating mutation in VHL.

From Clinical Diagnosis to the Discovery of Multigene Rare Sequence Variants in Pseudoxanthoma elasticum: A Case Report.

Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disease clinically characterised by early cutaneous alterations, and by late clinically relevant ocular, and cardiovascular manifestations. ABCC6 genetic tests are used to confirm clinical PXE diagnosis, but this strategy may be rather challenging when only one ABCC6 pathogenic variant is found. A next-generation sequencing approach focusing on 362 genes related to the calcification process and/or to inherited retinal diseases was performed on a patient with clinical PXE diagnosis (skin papules and laxity, angioid streaks, and atrophy) who was carrier of only one ABCC6 rare sequence variant. Beside ABCC6, several rare sequence variants were detected which can contribute either to the occurrence of calcification (GGCX and SERPINF1 genes) and/or to ophthalmological manifestations (ABCA4, AGBL5, CLUAP1, and KCNV2 genes). This wide-spectrum analysis approach facilitates the identification of rare variants possibly involved in PXE, thus avoiding invasive skin biopsy as well as expensive and time-consuming diagnostic odyssey and allows to broaden and to deepen the knowledge on this complex rare disease and to improve patients' counselling, also with a future perspective of personalised medicine.

Phenotypic Features and Genetic Findings in a Cohort of Italian Pseudoxanthoma Elasticum Patients and Update of the Ophthalmologic Evaluation Score.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare ectopic calcification genetic disease mainly caused by ABCC6 rare sequence variants. The clinical phenotype is characterized by typical dermatological, ophthalmological and cardiovascular manifestations, whose frequency and severity are differently reported in the literature. METHODS: A retrospective study was performed on 377 PXE patients of Italian origin, clinically evaluated according to the Phenodex Index, who underwent ABCC6 biomolecular analyses. Moreover, 53 PXE patients were further characterized by in-depth ophthalmological examinations. RESULTS: A total of 117 different ABCC6 rare sequence variants were detected as being spread through the whole gene. The severity of the clinical phenotype was dependent on age, but it was not influenced by gender or by the type of sequence variants. In-depth ophthalmological examinations focused on the incidences of coquille d'oeuf, comet lesions, pattern dystrophy-like lesions, optic disk drusen and posterior-pole atrophy. Conclusion: Given the large number of patients analyzed, we were able to better evaluate the occurrence of less frequent alterations (e.g., stroke, myocardial infarction, nephrolithiasis). A more detailed description of ophthalmological abnormalities allowed us to stratify patients and better evaluate disease progression, thus suggesting a further update of the PXE score system.

Clinical and molecular findings in patients with pattern dystrophy.

Purposes: To study the clinical and genetic background of a series of Italian patients affected by pattern dystrophy (PD).Methods: We reviewed patients with a clinical diagnosis of PD examined at the Eye Clinic in Florence from 2012 to 2019. We took into consideration patients with a standard ophthalmological examination, personal and familial ophthalmological history, fundus imaging, and molecular genetic analysis of genes PRPH2 and BEST1. We labelled patients with BEST1 and PRPH2 mutations as m-PD group (mutated) whereas patients with no mutations in these 2 genes as nm-PD group (non-mutated).Results: Seventy-seven PD patients were assessed (average age 59.7 ± 14.2, range 31-88 years). Fifty patients were placed in the nm-PD group and 27 in the m-PD. Pathogenic BEST1 and PRPH2 mutations were detected in 7% and 22% of PD patients, respectively. In total, we reported 1 BEST1 and 8 PRPH2 novel mutations. Ten patients were characterized by drusen in the nm-PD group whereas in no patients in the m-PD group drusen were detected at the fundus.Conclusions: An important proportion of patients affected by PD showed BEST1 or PRPH2 mutations. Patients affected by drusen represent a different sub-phenotype. Genetic examination is recommended for a correct clinical management.

Clinical and genetic findings in Italian patients with sector retinitis pigmentosa.

Purpose: To describe clinical and genetic features in a series of Italian patients with sector retinitis pigmentosa (sector RP). Methods: Fifteen patients with sector RP were selected from the database of Hereditary Retinal Degenerations Referring Center of Careggi Hospital (Florence, Italy). Eleven patients from five independent pedigrees underwent genetic analysis with next-generation sequencing (NGS) confirmed with Sanger sequencing. The diagnosis of sector RP was based on the detection of topographically limited retinal abnormalities consistent with corresponding sectorial visual field defects. Best-corrected visual acuity (BCVA), fundus color pictures as well as fundus autofluorescence (FAF), spectral domain-optical coherence tomography (SD-OCT), full-field electroretinography (ERG), and 30-2 Humphrey visual field (VF) data were retrospectively collected and analyzed. Results: For the 30 eyes, the mean BCVA was 0.05 ± 0.13 logMAR, and the mean refractive error was -0.52 ± 1.89 D. The inferior retina was the most affected sector (86.7%), and the VF defect corresponded to the affected sector. FAF showed a demarcation line of increased autofluorescence between the healthy and affected retina, corresponding on SD-OCT to an interruption of the ellipsoid zone (EZ) band in the diseased retina. Dark-adapted ERG amplitudes were decreased in comparison to normative values. In five unrelated families, the sector RP phenotype was associated with sequence variants in the RHO gene. The same mutation c.568G>A p.(Asp190Asn) was found in nine patients of four families. Conclusions: Typical sector RP is a mild form of RP characterized by preserved visual acuity with limited retinal involvement and, generally, a more favorable prognosis than other forms of RP.

Outer nuclear layer relevance in visual function correlated to quantitative enface OCT parameters in Stargardt disease.

PURPOSE: To evaluate the correlation between Best Corrected Visual Acuity (BCVA) and the following parameters in Stargardt Disease (STGD): Central Retinal Thickness (CR-T), Central Outer Nuclear Layer Thickness (C-ONL-T), Areas of macular Photoreceptor loss (PHRa), and Retinal Pigment Epithelium (RPE) loss (RPEa). METHODS: A total of 64 eyes of 32 STGD patients were included in the study. All patients received a comprehensive ophthalmological examination, color fundus photographs, fundus auto-fluorescence imaging, and Optical Coherence Tomography (OCT). The CR-T and C-ONL-T were evaluated from standard SD-OCT scans. The PHRa and RPEa were calculated from enface OCT scans (sub RPE slab and photoreceptor slab). The collected OCT parameters were evaluated for possible association with BCVA. RESULTS: The mean macular PHRa and RPEa was 16.16 ± 13.36 and 12.05 ± 12.57 mm2 respectively. The mean CR-T measured 120.78 ± 41.49 µm while the mean C-ONL-T was assessed at 4.60 ± 13.73 µm. BCVA showed the highest correlation with the C-ONL-T (r = -0.72; p < 0.001) while there was no correlation with the CR-T (r = -0.17; p = 1.00). CONCLUSIONS: Enface OCT permits a rapid and precise quantitative evaluation of the macular PHR and RPE atrophy area in STGD. Nonetheless, the OCT parameter that showed the highest correlation with visual acuity in STGD was the ONL thickness.

Subthreshold yellow micropulse laser for treatment of diabetic macular edema: Comparison between fixed and variable treatment regimen.

PURPOSE: To compare the efficacy between fixed and variable treatment regimens of subthreshold yellow micropulse laser for the treatment of diabetic macular edema. METHODS: This is a retrospective, comparative, 12-month study of 39 eyes: 24 eyes received fixed treatment regimen of subthreshold micropulse laser treatment and 15 eyes underwent variable treatment regimen of subthreshold micropulse laser, all eyes were followed up for 12 months. Subthreshold micropulse laser was performed with the following parameters: 100 µm spot size on slit lamp, 5% duty cycle of 0.2 s, and 250 mW power. To choose the power of the variable treatment regimen of subthreshold micropulse laser group, continuous laser power was titrated to a barely visible burn and then switched to MicroPulse mode, multiplying the test burn power by 4 and using a 5% duty cycle of 0.2 s. Main outcomes included changes in central macular thickness and best-corrected visual acuity. RESULTS: At baseline, the mean LogMAR best-corrected visual acuity was 0.297 ± 0.431 in the variable treatment regimen of subthreshold micropulse laser group and 0.228 ± 0.341 in the fixed treatment regimen of subthreshold micropulse laser group. At the end of follow-up, the mean LogMAR best-corrected visual acuity was 0.289 ± 0.473 (p = 0.785) and 0.245 ± 0.376 (p = 0.480) in the variable and fixed treatment regimens of subthreshold micropulse laser groups, respectively. Similarly, central macular thickness decreased in both groups after treatment; at baseline, the mean central macular thickness was 371.06 ± 37.8 in the variable treatment regimen of subthreshold micropulse laser group and improved to 325.60 ± 110.0 µm (p = 0.025) at the end of the follow-ups, while it was 342.30 ± 35.4 in the fixed treatment regimen of subthreshold micropulse laser group and improved to 308.51 ± 67.5 (p = 0.037). CONCLUSION: Both treatment regimens are effective for the treatment of mild center-involving diabetic macular edema: fixed treatment appears more suitable minimizing treatment time and reducing the possible errors due to wrong titration in the switch from continuous to micropulse mode.

CHOROIDAL VASCULARITY INDEX IN YOUNG CHOROIDEREMIA PATIENTS.

PURPOSE: To evaluate choroidal features in young patients affected by choroideremia (CHM). METHODS: Young CHM patients and control subjects were recruited at the Eye Clinic in Florence. High-resolution choroidal imaging was obtained using swept-source optical coherence tomography with long optical coherence tomography scans (12 × 9 mm optical coherence tomography scans). We considered the subfoveal choroidal area within 9 mm of the optic disk in the horizontal plane and the subfoveal choroidal area within a 3-mm diameter centered over the fovea. The subfoveal choroidal thickness, total choroidal area, luminal area, stromal area, and choroidal vascularity index were assessed using the "ImageJ" software in both groups. RESULTS: Eight patients (16 eyes; mean age, 19.3 ± 5.2 years) and seven control subjects (14 eyes; mean age, 19.0 ± 5.0 years) were included in this study. Best-corrected visual acuity was 20/20 in both eyes of seven CHM patients and in all control subjects and 20/25 in both eyes in one CHM patient. Mean subfoveal choroidal thickness did not differ between CHM patients and control subjects. Luminal area9mm, stromal area9mm, and total choroidal area9mm were reduced in patients compared with the control group. Luminal area3mm, stromal area3mm, and total choroidal area3mm did not differ between patients and control subjects. Choroidal vascularity index9mm and choroidal vascularity index3mm were not different between patients and control subjects. CONCLUSION: There are no differences in the choroidal vascularity index between young CHM patients and control subjects; this result suggests a simultaneous, proportional impairment of both the stromal and vascular components of the choroid in the early stages of the disease.

Acquired retinoschisis and vitreous hemorrhage as unusual findings in choroideremia: Case report.

PURPOSE: To report a case of choroideremia characterized by peripheral retinoschisis with vascular abnormalities and vitreous hemorrhage. OBSERVATIONS: A 58-year-old man affected by advanced-stage choroideremia was diagnosed with peripheral retinoschisis in both eyes. Vitreous hemorrhage was present in the right eye with a peculiar clot-like lesion at the periphery. At the 1-year follow-up, the vitreous hemorrhage had reabsorbed and the vascular clot-like lesion in the periphery had almost completely disappeared. CONCLUSION AND IMPORTANCE: We have reported fundoscopic and OCT features of peripheral-acquired retinoschisis with vascular abnormalities in a patient with choroideremia. OCT examination is extremely useful in clinical evaluation of the peripheral retinal alterations in these cases, where the absence of the retinal pigment epithelium and the choriocapillaris pose many diagnostic difficulties.

Adaptive Optics Imaging in Patients Affected by Pseudoxanthoma Elasticum.

PURPOSE: To describe the retinal findings of patients affected by pseudoxanthoma elasticum (PXE) using a multimodal imaging approach including flood-illumination adaptive optics ophthalmoscopy (AO). DESIGN: Retrospective case series. MATERIALS AND METHODS: Patients affected by PXE were retrospectively studied. Clinical data, color, infrared and autofluorescence fundus imaging, optical coherence tomographic scans, and AO examinations were collected. Furthermore, the photoreceptor count was assessed. PXE diagnosis was confirmed by a positive skin biopsy and/or genetic testing. RESULTS: Twenty-one eyes of 18 patients (11 females and 7 males) were included in the study. In 3 patients, both eyes were studied. The mean age at examination was 37.7 ± 16.4 years (range 14-66) and the mean best-corrected visual acuity (BCVA) was 0.1 ± 0.2 logMAR (range 0-1). We identified 3 types of angioid streaks (AS) using AO: "crack," "band," and "hypopigmented." The first 2 were very similar and they differed in size; the third type showed specific clinical features. Comet lesions appeared as hyper-reflective round lesions on AO imaging. In all eyes, the cone mosaic appeared reduced inside the streaks compared to the neighboring areas (13,532.8 ± 1,366.5 cones/mm2 vs 16,817.1 ± 1,263.0 cones/mm2 respectively). CONCLUSION: Using AO imaging in PXE-related retinopathy, we were able to observe the presence of the photoreceptors within the angioid streaks, differentiate 3 types of angioid streaks, based on size and reflective features, and identify the very small crystalline bodies not identifiable using other retinal imaging techniques.

Long-term follow-up and "double layer sign" in patients affected by circumscribed choroidal hemangioma.

BACKGROUND: Photodynamic therapy has revolutionised the treatment of circumscribed choroidal hemangiomas. The aim of this report is to report the long-term follow-up of patients affected by circumscribed choroidal hemangioma treated using photodynamic therapy. MATERIALS AND METHODS: We retrospectively reviewed patients affected by circumscribed choroidal hemangioma examined at the Retinal Medical Department at the Eye Clinic in Florence. We studied circumscribed choroidal hemangiomas treated using photodynamic therapy with at least 1 follow-up examination. Verteporfin was administered intravenously for 10 min (6 mg/m2 body surface area). After infusion (5 min), a 689 nm laser was applied with a light dose of 50 J/cm2. RESULTS: Ten eyes of 10 patients with circumscribed choroidal hemangioma who underwent Photodynamic therapy were included in our series (2 females and 8 males; average age at diagnosis 47.8 ± 9.3 yrs.; age range: 27-56 years). Five patients (5/10; 50 %) received only the photodynamic treatment whereas 5 patients (5/10; 50 %) also received other treatments (laser photocoagulation, intravitreal injection). On average, the patients received 2 photodynamic treatments (range 1-4). Four patients (4/10, 40 %) had a > 5-year follow-up; (average 4.5 ± 3.7 yrs. range 6 months - 10 years). In 2 patients we identified the "double layer sign" at the optical coherence tomography examination on circumscribed choroidal hemangioma. CONCLUSIONS: In our series, photodynamic therapy was a safe and effective treatment for circumscribed choroidal hemangioma during long-term follow-up. The double layer sign, which can be detected in several choroidal pathologies, suggests common pathogenetic mechanisms for circumscribed choroidal hemangiomas and central serous chorioretinopathy/polypoidal choroidopathy spectrum disease.

Optical coherence tomography angiography cyclic remodeling of CNV in patients affected by Best macular dystrophy.

PURPOSE: To evaluate the effect of photodynamic therapy and/or intravitreal injections on choroidal neovascularization in treatment-naïve patients affected by Best Macular Dystrophy using OCT-A. MATERIALS AND METHODS: BMD patients with CNV treated using PDT and/or IV were included in the study. All patients underwent a complete ophthalmological examination, OCT and 3 × 3 mm OCT-A. The OCT-A images were analyzed using an open-source software (ImageJ) to assess the CNV membrane area (CNV-MA), the CNV vessel area (CNV-VA), and vessel density (VD) at the follow-ups (3 months after PDT and 1 month after IV). RESULTS: Five eyes of four patients with CNV were included. All eyes received PDT as first-line therapy; 4 eyes underwent more than 1 treatment session: three eyes received 1 IV, whereas one eye had one further PDT. After PDT, the CNV-MA, CNV-VA, and VD quantitative parameters were obtained for four out of five eyes: in three eyes of two patients CNV-MA, CNV-VA, and VD first decreased and then gradually increased during follow-up, whereas in one eye of one patient CNV-MA, CNV-VA, and VD slightly increased. After IV the CNV-MA, CNV-VA, and VD had significantly decreased at the 1-month follow-up in three eyes of three patients. CONCLUSION: OCT-A is an important tool for the diagnosis of both naïve and fibrotic CNV in BMD patients; it is a non-invasive method for the qualitative and quantitative analysis of neovascular lesions during follow-up. Our results have shown a cyclic remodeling of treated CNV in BMD patients using both PDT and IV.

Pattern dystrophy-like changes and coquille d'oeuf atrophy in elderly patients affected by pseudoxanthoma elasticum.

PURPOSE: To evaluate the retinal features of elderly patients affected by pseudoxanthoma elasticum (PXE). MATERIALS AND METHODS: This is a retrospective case series of 62 eyes of 31 elderly PXE patients (age > 50 years). Clinical data, ultra-widefield fundus imaging (color, red-free (RF), infra-red imaging (IR), fundus autofluorescence (FAF)), and OCT examinations were collected. Diagnosis was confirmed by genetic testing or skin biopsy. RESULTS: Thirty-one patients (10 males and 21 females (mean age 61.3 years, range 50-74 years)) were included in our study. Visual acuity ranged from 20/20 Snellen equivalent to 20/200. The mean follow-up was 66.4 ± 20.7 months (range 10-88). Pattern dystrophy-like changes (PD) (52 eyes of 26 patients, 83.8%) and atrophy resembling the "diffuse trickling" pattern described in geographic atrophy were present in the majority of patients. Twenty-three eyes of 12 patients (67.6%) had peripapillary atrophy, 9 eyes of 5 patients (26.4%) macular atrophy, 6 eyes of 3 patients (17.6%) displayed posterior pole atrophy and in 6 eyes of 3 patients (17.6%), atrophy could be detected beyond the vascular arcades (mid-peripheral atrophy). End-stage atrophy covered the entire area indicated as "coquille d'oeuf" (eggshell). Choroidal neovascularization occurred in 49 eyes of 26 patients (94.2%) with PD and in 6 eyes of 3 patients (60%) without PD. Genetic examinations were available for 29 patients (29/31, 93.5%). CONCLUSIONS: The elderly PXE patients were characterized by pattern dystrophy-like changes with more or less extensive atrophy, progressive over time, which in some cases affected the whole area of the coquille d'oeuf during the course of the disease.