Atypic Retinitis Pigmentosa Clinical Features Associated with a Peculiar CRX Gene Mutation in Italian Patients.

Purpose: To describe an atypical phenotypic pattern of late-onset retinitis pigmentosa (RP) due to the same specific c.425A>G (p.Tyr142Cys) heterozygous mutation in the cone-rod homeobox gene (CRX gene) in two unrelated Italian patients. Case 1: A 67-year-old woman (P.P.) was incidentally diagnosed with sector RP at the age of 50. The patient was initially asymptomatic and did not have any family history of retinal dystrophy. Fundus examination showed the presence of typical retinal pigmentary deposits with a peculiar pericentral/sector distribution. Genomic sequencing disclosed the missense mutation c.425A>G (p.Tyr142Cys) in the CRX gene. During the follow-up period of 7 years, the patient maintained good visual acuity and complained only of mild symptoms. Case 2: A 76-year-old man (P.E.) presented with nyctalopia and visual field constriction since the age of 50. Fundus examination showed the presence of retinal pigment deposits with a concentric pericentral and perimacular pattern. A full-field electroretinogram (ffERG) showed extinguished scotopic responses and reduced abnormal photopic and flicker cone responses. Genomic sequencing identified the same missense mutation, c.425A>G (p.Tyr142Cys), in the CRX gene. Similarly to the first case, during the whole follow-up of 7 years, the visual acuity remained stable, as did the visual field and the patient's symptoms. Conclusions: We report the first cases of late-onset retinitis pigmentosa related to a specific heterozygous CRX gene mutation in exon 4. We also report two atypical phenotypic RP patterns related to mutations in the CRX gene.

An in silico toolbox for the prediction of the potential pathogenic effects of missense mutations in the dimeric region of hRPE65.

hRPE65 is a fundamental enzyme of the retinoid visual cycle, and many missense mutations affecting its expression or function are associated with a wide range of diseases. Many hRPE65 missense mutations lack a clear pathogenicity classification or are labelled as VUS. In this context, we recently developed a protocol based on µs-long molecular dynamics simulations to study the potential pathogenic effect of hRPE65 missense mutations. In the present work, the structure-based protocol was integrated with a hRPE65-tailored consensus bioinformatics strategy, named ConPath, that showed high performance in predicting known pathogenic/benign hRPE65 missense mutations. The combined strategy was used to perform a multi-level evaluation of the potential pathogenicity of 13 different hRPE65 VUS, which were classified based on their likelihood of pathogenic effect. The obtained results provide information that may support the reclassification of these VUS and help clinicians evaluate the eligibility for gene therapy of patients diagnosed with such variants.

Choroidal vascularity index in eyes with central macular atrophy secondary to age-related macular degeneration and Stargardt disease.

PURPOSE: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI). METHODS: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 µm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts. RESULTS: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 µm vs 353 ± 105 µm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old. CONCLUSION: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response.

Predicting potentially pathogenic effects of hRPE65 missense mutations: a computational strategy based on molecular dynamics simulations.

The human retinal pigment epithelium-specific 65-kDa protein (hRPE65) plays a crucial role within the retinoid visual cycle and several mutations affecting either its expression level or its enzymatic function are associated with inherited retinal diseases such as Retinitis Pigmentosa. The gene therapy product voretigene neparvovec (Luxturna) has been recently approved for treating hereditary retinal dystrophies; however, the treatment is currently accessible only to patients presenting confirmed biallelic mutations that severely impair hRPE65 function, and many reported hRPE65 missense mutations lack sufficient evidences for proving their pathogenicity. In this context, we developed a computational approach aimed at evaluating the potential pathogenic effect of hRPE65 missense variants located on the dimerisation domain of the protein. The protocol evaluates how mutations may affect folding and conformation stability of this protein region, potentially helping clinicians to evaluate the eligibility for gene therapy of patients diagnosed with this type of hRPE65 variant of uncertain significance.

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.

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.

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.

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.

IN VIVO OBSERVATION OF RETINAL VASCULAR DEPOSITS USING ADAPTIVE OPTICS IMAGING IN FABRY DISEASE.

PURPOSE: To report a novel finding in patients with Fabry disease, that is, the observation by adaptive optics ophthalmoscopy of intracellular lipidic deposits in retinal vessels. METHODS: Observational two-center case series. Eighteen patients with genetically proven Fabry disease underwent flood-illumination adaptive optics ophthalmoscopy imaging (rtx1; Imagine Eyes, Orsay, France) of retinal vessels. RESULTS: Fourteen patients (78% of all patients; 7 of the 10 women and 7 of the 8 men) showed paravascular punctuate or linear opacities in both eyes. In the least-affected patients, these were seen only in the wall of precapillary arterioles as discrete spots of 5 µm to 10 µm large, whereas in those more severely affected, capillaries and first-order vessels were also involved with diffuse opacification of the wall. These deposits sometime showed a striated pattern, suggesting colocalization with vascular smooth muscle cells. CONCLUSION: Adaptive optics ophthalmoscopy of retinal vessels may be of interest for patients with Fabry disease, providing noninvasive, gradable evaluation of microvascular involvement.

Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa: A Multicenter Safety Study of the OkuStim® System (TESOLA-Study).

BACKGROUND: Transcorneal electrical stimulation (TES) has been suggested as a possible treatment for retinitis pigmentosa (RP). OBJECTIVE: To expand the safety assessment of repeated applications of an electrical current from a DTL-like electrode in patients with RP. METHODS: This single-arm open label interventional safety trial included a total of 105 RP patients from 11 European centers, who received weekly TES for 6 months on 1 eye followed by observation for another 6 months without stimulation. The primary outcome measure was safety, indicated by the frequency and severity of adverse events. Secondary measures included intraocular pressure and central retinal thickness. Visual field and visual acuity were examined using the methods available at each site. RESULTS: Dry eye sensation was the most common adverse event recorded (37.5%). Serious adverse events secondary to TES were not observed. Most adverse events were mild and all resolved without sequelae. The secondary outcome measures revealed no significant or clinically relevant changes. CONCLUSION: The present results confirm the excellent safety profile of TES. Transient dry eye symptoms were the most common adverse event.

Novel clinical findings in autosomal recessive NR2E3-related retinal dystrophy.

PURPOSE: To evaluate the clinical phenotype of autosomal recessive NR2E3-related retinal dystrophy. METHODS: We retrospectively studied 11 patients carrying out at least 2 NR2E3 mutations; they had undergone comprehensive ophthalmological examination, fundus photography, optical coherence tomography, electrophysiological testing, and visual field at the Regional Reference Center for Hereditary Retinal Degenerations of the Eye Clinic in Florence. RESULTS: Five females and six males with a diagnosis of NR2E3-related retinal dystrophy were included in the study. All patients complained of nyctalopia. Visual acuity ranged from 0.00 logMAR to hand motion. Two patients presented bull's eye maculopathy, and one of these was characterized by a triple hyper-autofluorescent ring at the fundus autofluorescence examination. Three patients showed small yellowish dots and spots at the mid-periphery. One patient was characterized by widespread subretinal drusenoid deposits (SDD) at the posterior pole. Four patients showed vitreous abnormalities. Optical coherence tomography (OCT) examinations detected variable degrees of abnormal retinal lamination and schitic changes. Seven patients were compound heterozygous and four were homozygous for mutations in NR2E3. CONCLUSIONS: Our study confirmed high variable phenotype in autosomal recessive NR2E3-related retinal dystrophy. Bull's eye maculopathy, subretinal drusenoid deposits, and foveal hypoplasia represent novel clinical findings in NR2E3-related retinal dystrophy. Macular involvement was detectable in all the patients, and the abnormal foveal avascular zone (FAZ) supports the role of NR2E3 in retinal development.

Optical coherence tomography (OCT) features of cystoid spaces in choroideremia (CHM).

PURPOSE: To investigate the prevalence and features of cystoid spaces (CS) in patients with confirmed genetic diagnosis of choroideremia (CHM) using swept source optical coherence tomography (OCT). METHODS: We retrospectively reviewed CHM patients examined at the Regional Reference Center for Hereditary Retinal Degenerations at the Eye Clinic in Florence. We took into consideration genetically confirmed CHM patients with ophthalmological and swept source optical coherence tomography (OCT) examinations. The presence/absence and location of cystoid spaces in the retina of each eye were reported. RESULTS: A total of 42 eyes of 21 CHM patients were included in our series. The average age of the patients was 36.5 ± 20.1 (range, 13-73 years). The average best-corrected visual acuity (BCVA) for all patients was 0.63 ± 1.00 logMar (range, 0-2,80). CS were present in 15 eyes of eight patients (8/21, 38%). In all cases, CS were located in inner nuclear layer (INL); in five eyes of three patients, CS were detected also in ganglion cell layer (GCL). CS appeared as microcistoyd abnormalities and were detected in retinal areas characterized by retinal pigment epithelium (RPE) and outer retinal layers atrophy at the transition zone. CONCLUSIONS: Cystoid spaces in choroideremia showed peculiar features; they are clusters of small-size extrafoveal degenerative cysts mainly located in inner nuclear layer at the transition zone where outer retinal layers and RPE are severely damaged.

Peculiar Clinical Findings in Young Choroideremia Patients: A Retrospective Case Review.

PURPOSE: To report peculiar clinical findings in young choroideremia (CHM) patients. METHODS: We retrospectively reviewed young (age <20 years at the first evaluation) CHM patients examined at the Regional Reference Center for Hereditary Retinal Degenerations at the Eye Clinic in Florence between 2012 and 2018. We took into consideration patients with ophthalmological examinations, fundus color photographs, fundus autofluorescence (FAF) images, optical coherence tomography (OCT) scans, full-field electroretinograms, and Goldmann visual fields. RESULTS: In our series, we studied 8 young CHM patients (average age 13.8 years, median age 12.5, range 10-20) for a total of 16 eyes. Visual acuity (VA) was 20/20 in 7 patients and 20/25 in both eyes of 1 patient. We identified a peculiar central FAF pattern (detectable in 3 patients), characterized by reduced central hypo-autofluorescence. Long OCT scans showed different forms of parapapillary retinal involvement from the mildest to the most severe form when the macula is still preserved. In 3 patients, at the time of atrophic changes at the posterior pole, it was possible to detect a progressive reduction of foveal pigmentation during follow-up. We found mutations of the CHM gene in all 6 patients who had been screened. CONCLUSIONS: CHM is a progressive retinal disorder which involves both the peripheral and the central retina. Using a multimodal imaging approach, we described peculiar central abnormalities underlying the early involvement of the central retina in young CHM patients with a good VA.

Peripapillary comet lesions and comet rain in PXE-related retinopathy.

PURPOSE: To study peripapillary comet lesions (PCL) in Italian patients affected with pseudoxanthoma elasticum (PXE). METHODS: Retrospective review of fundoscopic and swept-source (SS) optical coherence tomography (OCT) images of patients with PXE examined at the Regional Reference Center for Hereditary Retinal Degenerations at the Careggi Teaching Hospital of Florence from 2012 to 2017. RESULTS: From 148 eyes of 74 patients affected with PXE, we identified 24 eyes of 14 patients (11 were female) with a mean age of 39 years (range, 20-58 years) characterized by peripapillary comet lesions. Of these 24 eyes, 15 eyes (of 10 patients) were characterized by comet rain. The smallest comet lesion at the OCT examination appeared as a focal roundish hyper-reflective alteration at the level of the outer retinal segments and RPE-Bruch's membrane complex; the larger lesions appeared as circular and ovoid structures with hyper-reflective borders in the outer nuclear layer. CONCLUSION: The comet lesion formation process involves the outer layers of the retina and RPE/Bruch's membrane complex. It consists of a degenerative/rearrangement process of the photoreceptors which occurs in an area of focal altered RPE/Bruch's membrane resembling the outer retinal tubulation.

Retinal dystrophy and subretinal drusenoid deposits in female choroideremia carriers.

PURPOSE: To describe clinical and molecular characteristics in a group of Italian female choroideremia (CHM) carriers and report fundus patterns. METHODS: We retrospectively studied 11 female carriers belonging to six CHM families examined at the Regional Reference Center for Hereditary Retinal Degenerations at the Eye Clinic in Florence. We took into consideration patients with a comprehensive ophthalmological examination, fundus photography, optical coherence tomography (OCT), full field electro-retinography (ERG), and visual field (VF). All patients were screened for mutations of the CHM gene. RESULTS: Fundus examination revealed retinal abnormalities in all female carriers (11/11) in the study; in particular four fundus patterns were identified: pattern A (RPE dystrophy involving only the peripheral retina), pattern B (RPE dystrophy involving the peripheral retina and the posterior pole with small hypo-pigmented RPE areas), pattern C (RPE dystrophy involving the peripheral retina and the posterior pole with small yellowish well-defined dots), and pattern D (RPE dystrophy involving the peripheral retina and the posterior pole with large hypo-pigmented RPE areas and well-defined yellowish dots). Pattern D was characterized by widespread macular subretinal drusenoid deposits (SDD). Half of the observed mutations were novel mutations. A genotype-phenotype correlation was not identified. CONCLUSIONS: Retinal dystrophy and SDD were detected in our female CHM carriers, and fundus patterns have been described in this study. The recognition of specific fundoscopic patterns may permit a correct diagnosis, an appropriate molecular investigation and genetic counseling.

Multimodal analysis of the Preferred Retinal Location and the Transition Zone in patients with Stargardt Disease.

PURPOSE: The purpose of our study was to investigate morpho-functional features of the preferred retinal location (PRL) and the transition zone (TZ) in a series of patients with recessive Stargardt disease (STGD1). METHODS: Fifty-two STGD1 patients with at least one ABCA4 mutation, atrophy of the central macula (MA) and an eccentric PRL were recruited for the study. Microperimetry, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) were performed. The location and stability of the PRL along with the associated FAF pattern and visual sensitivities were determined and compared to the underlying retinal structure. RESULTS: The mean visual sensitivity of the PRLs for the 52 eyes was 10.76 +/- 3.70 dB. For the majority of eyes, PRLs were associated with intact ellipsoid zone (EZ) bands and qualitatively normal FAF patterns. In 17 eyes (32.7%) the eccentric PRL was located at the edge of the MA. In 35 eyes (67.3%) it was located at varying distances from the border of the MA with a TZ between the PRL and the MA. The TZ was associated with decreased sensitivity values (5.92 +/- 4.69 dB) compared to PRLs (p<0.05), with absence/disruption of the EZ band and abnormal FAF patterns (hyper or hypo-autofluorescence). CONCLUSIONS: In STGD1 eccentric PRLs are located away from the border of MA and associated with intact EZ bands and normal FAF. The TZ is characterized by structural and functional abnormalities. The results of multimodal imaging of the PRL and TZ suggest a possible sequence of retinal and functional changes with disease progression that may help in the planning of future therapies; RPE dysfunction appears to be the primary event leading to photoreceptor degeneration and then to RPE loss.

COMPUTER ASSISTED RETINAL VESSEL TORTUOSITY EVALUATION IN NOVEL MUTATION FABRY DISEASE: Towards New Prognostic Markers.

PURPOSE: Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. METHODS: Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. RESULTS: Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. CONCLUSION: p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.

Case report of an atypical early onset X-linked retinoschisis in monozygotic twins.

BACKGROUND: X-linked Retinoschisis (XLRS) is one of the most common macular degenerations in young males, with a worldwide prevalence ranging from 1:5000 to 1:20000. Clinical diagnosis of XLRS can be challenging due to the highly variable phenotypic presentation and limited correlation has been identified between mutation type and disease severity or progression. CASE PRESENTATION: We report the atypical early onset of XLRS in 3-month-old monozygotic twins. Fundus examination was characterized by severe bullous retinal schisis with pre-retinal and intraretinal haemorrhages. Molecular genetic analysis of the RS1 was performed and the c.288G > A (p. Trp96Ter) mutation was detected in both patients. CONCLUSIONS: Early onset XLRS is associated with a more progressive form of the disease, characterized by large bullous peripheral schisis involving the posterior pole, vascular abnormalities and haemorrhages. The availability of specific technology permitted detailed imaging of the clinical picture of unusual cases of XLRS. The possible relevance of modifying genes should be taken into consideration for the future development of XLRS gene therapy.

Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment.

PURPOSE: To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) drugs with a pro re nata (PRN) regimen for the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). METHODS: This is a retrospective, multicenter, noncomparative case series of consecutive AS eyes affected by treatment-naïve CNV. A complete ophthalmologic examination was performed every 30-45 days after the loading phase, including fluorescein angiography and/or optical coherence tomography. RESULTS: In all, 52 eyes of 39 patients were treated with intravitreal bevacizumab and/or ranibizumab and followed up for a mean of 33.8 months. The best corrected visual acuity at baseline was 20/40, and it deteriorated by an average of 6.8 ETDRS letters per year (p < 0.001). We performed an average of 5.1, 6.5, and 6.8 injections at the 1-, 2-, and 3-year follow-up, respectively. CONCLUSIONS: Intravitreal anti-VEGF drugs in a PRN regimen with close monitoring appear to slow the progression of CNV in AS, but they do not prevent the affected eyes from progressive visual loss.