Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis.

BACKGROUND: Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings. METHODS: This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established. RESULTS: Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings. CONCLUSIONS: This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.

Predicting retinal pigment epithelium remodelling and its functional impact.

PURPOSE: To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. METHODS: Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. RESULTS: This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 µm, p=0.02; width 2379 vs. 3378 µm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). CONCLUSION: RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

Incidence of endophthalmitis after intravitreal injection with and without topical antibiotic prophylaxis.

PURPOSE: The purpose was to compare the incidence of endophthalmitis after intravitreal injection with and without topical antibiotic prophylaxis. METHODS: This is a single-center, retrospective case-control study. All patients treated with intravitreal injection of ranibizumab, bevacizumab, aflibercept, or corticosteroids for a variety of retinal vascular diseases between 1 October 2014 and 30 November 2018 were included. The total number of patients and injections were determined from a review of billing code and practice management records. Endophthalmitis cases were determined from billing records and then confirmed with chart review. A 24-month period when topical antibiotics were prescribed after intravitreal injection was compared with a 24-month period when topical antibiotics were not prescribed. RESULTS: Between 1 October 2014 and 30 November 2018, a total of 33,515 intravitreal injections were performed and 13 cases of post-intravitreal injection endophthalmitis were identified (incidence rate of 0.0388%; 95% confidence interval, 0.0217%-0.0644%) or approximately 1 case for every 2578 intravitreal injections. Between 1 October 2014 and 31 October 2016, while topical antibiotic prophylaxis was used postoperatively, 14,828 intravitreal injections were performed and 5 cases of endophthalmitis were reported (0.0337%; 95% confidence interval, 0.0129%-0.0739%). Between 1 November 2016 and 30 November 2018, while no prophylaxis was used, 18,687 intravitreal injections were performed and 8 cases of endophthalmitis were identified (0.0428%; 95% confidence interval, 0.0202%-0.0808%). There were no statistical differences in the incidence rates between the two groups (p = 0.675). CONCLUSION: The incidence rate of endophthalmitis in the group with topical antibiotic prophylaxis after intravitreal injection was similar to the group with no prophylaxis. Changing the current clinical practice to no antibiotic prophylaxis had no effect on the incidence of endophthalmitis.

WAGNER syndrome: anatomic, functional and genetic characterization of a Portuguese family.

PURPOSE: To report the clinical (anatomic and functional) and genetic findings of Wagner Syndrome (WS) in a Portuguese family. METHODS: Nine members of the family agreed to be examined. All had complete clinical eye examinations. The proband and selected patients underwent color fundus photography, spectral domain optical coherence tomography (SD-OCT), automatic static white-on-white computerized perimetry, and electrophysiology assessment (flash ERG, multifocal(mf) ERG and dark adaptometry). A pedigree was constructed based on interviews with known affected subjects. Genomic DNA samples derived from venous blood were collected from all affected family members examined. RESULTS: Twenty-eight family members are affected. This family has the typical features of Wagner Syndrome, namely an empty vitreous cavity with veils, mild myopia and cataract. Four examined patients underwent vitreoretinal surgery due to abnormal peripheral vitreoretinal adhesions with peripheral retinal traction (n = 3). Retinal detachment was observed in 5 of the examined subjects. Four of them occurred between the ages of 5 and 15 years. Chorioretinal atrophy is also a frequent finding which results in moderate to severe visual field and advanced rod-cone dystrophy from younger ages, also confirmed by absence of scotopic function on dark adaptation. The macular dysfunction on mfERG was profound and of early onset. A heterozygous mutation in intron 7 of the VCAN gene (c.4004-1G > A) was found. CONCLUSIONS: We described a rare autosomal dominant vitreoretinopathy with near complete penetrance in a Portuguese family. Abnormal peripheral vitreoretinal adhesions, retinal detachment and chorioretinal atrophy are present in most of the examined individuals at young ages. Early onset of advanced visual field and electrophysiologic abnormalities were observed in this family. We also added relevant information to the literature by reporting our experience in surgical management of Wagner Syndrome patients with, and at risk of, retinal detachment.

Safety and Effectiveness of Cataract Surgery with Simultaneous Intravitreal Anti-VEGF in Patients with Previously Treated Exudative Age-Related Macular Degeneration.

INTRODUCTION: To evaluate the safety and impact on visual acuity, retinal and choroidal morphology of simultaneous cataract surgery and intravitreal anti-vascular endothelial growth factor on patients with visually significant cataracts and previously treated exudative age-related macular degeneration. MATERIAL AND METHODS: Prospective study, which included 21 eyes of 20 patients with exudative age-related macular degeneration submitted to simultaneous phacoemulsification and intravitreal ranibizumab or bevacizumab. The patients were followed for 12 months after surgery using a pro re nata strategy. Visual acuity, foveal and choroidal thickness changes were evaluated 1, 6 and 12 months post-operatively. RESULTS: There was a statistically significant increase in mean visual acuity at one (13.4 letters, p < 0.05), six (11.5 letters, p < 0.05) and twelve months (11.3 letters, p < 0.05) without significant changes in retinal or choroidal morphology. At 12 months, 86% of eyes were able to maintain visual acuity improvement. There were no significant differences between the two anti-vascular endothelial growth factor drugs and no complications developed during follow-up. DISCUSSION: Simultaneous phacoemulsification and intravitreal anti- vascular endothelial growth factor is safe and allows improvement in visual acuity in patients with visually significant cataracts and exudative age-related macular degeneration. Visual acuity gains were maintained with a pro re nata strategy showing that in this subset of patients, phacoemulsification may be beneficial. CONCLUSION: Cataract surgery and simultaneous anti-vascular endothelial growth factor therapy improves visual acuity in patients with exudative age-related macular degeneration.

Introdução: Pretendemos avaliar a efectividade e segurança da cirurgia de catarata associada a injecção intravítrea de anti-vascular endothelial growth factor sobre a acuidade visual, morfologia da retina e coróide em doentes previamente tratados por degeneração macular relacionada com a idade exsudativa com cataratas visualmente significativas. Material e Métodos: Estudo prospectivo, que incluiu 21 olhos de 20 doentes com degeneração macular relacionada com a idade exsudativa submetidos a facoemulsificação simultânea com ranibizumab ou bevacizumab intravítreo. Os doentes foram seguidos durante 12 meses após a cirurgia usando uma estratégia pro re nata. As alterações da acuidade visual, espessura da retina e coroideia subfoveal foram avaliadas aos 1, 6 e 12 meses de pós-operatório. Resultados: Houve um aumento estatisticamente significativo da acuidade visual média ao mês (13,4 letras, p < 0,05), aos seis (11,5 letras, p < 0,05) e doze meses (11,3 letras, p < 0,05), sem alterações significativas na morfologia da retina ou coróide. Aos 12 meses, 86% dos olhos foram capazes de manter a melhoria da acuidade visual. Não houve diferenças significativas entre os dois fármacos anti-vascular endothelial growth factor e não ocorreu qualquer complicação durante o seguimento. Discussão: A facoemulsificação associada a injecção intravítrea de anti-vascular endothelial growth factor é segura e permite uma melhoria da acuidade visual em doentes com degeneração macular relacionada com a idade exsudativa e cataratas visualmente significativas. O ganho de acuidade visual foi mantido usando uma estratégia pro re nata mostrando que neste subgrupo de doentes a facoemulsificação pode ser benéfica. Conclusão: A cirurgia de catarata associada a terapia anti-vascular endothelial growth factor simultânea melhora a acuidade visual em doentes com degenerescência macular da idade exsudativa.

Combined treatment with intravitreal bevacizumab and laser photocoagulation for exudative maculopathy in facioscapulohumeral muscular dystrophy.

PURPOSE: To report a rare case of exudative maculopathy in a patient with facioscapulohumeral muscular dystrophy (FSHD), and its management. METHODS: Observational case report. RESULTS: A 62-year-old man with genetically confirmed FSHD was referred to our department complaining of decreased visual acuity in his left eye. At presentation, right eye examination was unremarkable and best-corrected visual acuity (BCVA) was 20/20. Left eye BCVA was 20/100 and it presented a dense cataract with the evidence of macular lipid exudation. Cataract surgery combined with intravitreal bevacizumab improved BCVA to 20/20. Postoperative fundus examination disclosed focal macular retinal microvascular dilations with lipid exudation inferotemporal to the fovea. Fluorescein angiography highlighted these macular telangiectatic abnormalities but no peripheral lesions were detected. Spectral domain optical coherence tomography (SD-OCT) showed mild temporal retinal thickening, sparing the fovea. A diagnosis of exudative maculopathy due to macular telangiectasia secondary to FSHD was established. One year later, his left eye vision dropped to 20/32 and macular SD-OCT showed an aggravation of the intraretinal fluid and exudation. He was then submitted to a second intravitreal injection of bevacizumab followed by one angio-guided focal laser photocoagulation session, with a significant improvement. Twelve months later, his BCVA remained 20/20 on both eyes with no recurrence of exudation. CONCLUSION: The present work shows that in cases of visual-threatening macular exudation, intravitreal anti-vascular endothelial growth factor injections combined with focal laser photocoagulation may be a safe and effective treatment. This article also highlights that all FSHD patients should be screened for asymptomatic retinal vascular disorders.

Switch to Aflibercept in the Treatment of Neovascular AMD: One-Year Results in Clinical Practice.

PURPOSE: To report the clinical outcomes of intravitreal aflibercept therapy in eyes with refractory and recurrent neovascular age-related macular degeneration (AMD) switched from intravitreal bevacizumab or ranibizumab. METHODS: This is a retrospective review of eyes with neovascular AMD switched to intravitreal aflibercept with at least 1 year of follow-up after the switch. All patients had had a minimum of 3 injections of bevacizumab or ranibizumab before the switch. Aflibercept was used in patients considered refractory to bevacizumab (group 1) and in recurrent patients on therapy with ranibizumab due to an institutional policy decision (group 2). Changes in best-corrected visual acuity, fluid on optical coherence tomography (OCT), central retinal thickness (CRT) and the frequency of injections were compared. RESULTS: Eighty-five eyes of 69 patients were analyzed, 39 eyes in group 1 and 46 in group 2. The mean follow-up time was 31.6 months prior to the switch and 14.7 months on treatment with aflibercept. One year after the switch, there was a nonsignificant mean decrease of 2 letters in visual acuity in both groups (group 1: from 58.2 to 55.8 letters, p = 0.086; group 2: from 56.4 to 54.5 letters, p = 0.168), but the mean number of injections per month was significantly lower (from 0.76 to 0.57, p < 0.001). With the switch, 90.6% of the patients showed anatomic improvement with a reduction of fluid on OCT, and both groups presented significant improvement in CRT (group 1: 65.3 µm, p = 0.051; group 2: 91.0 µm, p < 0.001). CONCLUSION: Aflibercept appears to be a valuable tool for the management of patients with poor responses to other anti-vascular endothelial growth factor drugs. These patients could have anatomic improvement, and the injection intervals could be extended.

Multimodal imaging in paclitaxel-induced macular edema: the microtubule disfunction.

Taxanes are a rare cause of macular edema. A 63-year-old female, under paclitaxel treatment, was observed with progressively bilateral visual acuity loss and an apparently normal fundus. Optical coherence tomography revealed a bilateral cystoid macular edema with a late petaloid pooling on fluorescein angiography. Fundus autofluorescence exhibited a foveal hiperautofluorescent pattern. There was a great improvement of visual acuity and macular thickness after 5 months of drug withdrawal. Paclitaxel maculopathy diagnosis requires a high degree of suspicion. The pathophysiology remains unclear.

Comparison of topical dorzolamide and ketorolac treatment for cystoid macular edema in retinitis pigmentosa and Usher's syndrome.

PURPOSE: To investigate the topical effect of dorzolamide versus ketorolac on retinitis pigmentosa (RP) and Usher's syndrome (US) macular edema. METHODS: Prospective, randomized and interventional study. A total of 28 eyes of 18 patients were included. Five eyes had US, 23 had RP. Fifteen eyes were allocated to ketorolac tromethamine 0.5% (4 drops daily regimen) and 13 eyes to dorzolamide hydrochloride 2% (3 drops daily regimen) treatment groups. Snellen's best-corrected visual acuity (BCVA), foveal thickness (FT) and foveal zone thickness (FZT) measured by Stratus® optical coherence tomography (OCT) were evaluated at baseline, 1, 3, 6 and 12 months after treatment. RESULTS: Patients assigned to ketorolac had a baseline BCVA of 0.37 ± 0.17 logMAR which improved at the end of 1 year to 0.28 ± 0.16 (p = 0.02). Three eyes (20%) of 2 patients improved by 7 letters or more. Mean FT and FZT did not change significantly during the study follow-up. After 1 year of treatment, 4 eyes (27%) of 3 patients showed an improvement of at least 16% of FT and 11% of FZT. Patients assigned to dorzolamide had a baseline BCVA of 0.48 ± 0.34 logMAR which improved in the first 6 months (0.40 ± 0.30; p = 0.01), with a decrease at 1 year (0.42 ± 0.27; p = 0.20). Seven eyes (54%) of 5 patients had an improvement of 7 letters or more. Mean FT and FZT did not change significantly either. After 1 year of treatment, 3 eyes (23%) of 2 patients showed an improvement of at least 16% on FT and 11% on FZT. CONCLUSIONS: RESULTS suggest that dorzolamide and ketorolac might improve visual acuity and therefore be of interest in selected cases. No relationship between retinal thickness fluctuation and visual acuity was found. Sample size was a limitation to the study.

Evaluation of visual acuity, macular status, and subfoveal choroidal thickness changes after cataract surgery in eyes with diabetic retinopathy.

PURPOSE: Progression of diabetic macular edema has been reported as a common cause of poor visual acuity recovery after cataract surgery in patients with diabetes. Despite being responsible for the blood supply to the outer retina, the role of the choroidal layer in the pathogenesis of diabetic retinopathy (DR) is not yet understood. Our objective is to characterize macular and subfoveal choroidal thickness changes after cataract surgery in eyes with DR. METHODS: Thirty-five eyes with clinically significant cataract of patients with DR were divided into three groups based on clinical and optical coherence tomography findings: patients with DR without macular edema, patients with DR and macular thickening detected on optical coherence tomography, and finally patients with clinically significant macular edema. All cases were submitted to ophthalmologic examination and spectral domain optical coherence tomography 1 week before cataract surgery and repeated 1 month after surgery. Patients with preoperative clinically significant macular edema were treated with intravitreal bevacizumab at the time of surgery. RESULTS: All groups showed a significant increase in visual acuity 1 month after surgery (P < 0.001). Mean foveal thickness increased significantly in all groups, including controls (P = 0.013), except in patients who were simultaneously treated with intravitreal bevacizumab (P = 0.933). An increase of maximum macular thickness of at least 11% was found in 25.7% of the DR eyes, but no such increase occurred in the control eyes. No significant change was verified for subfoveal choroidal thickness in any of the studied groups. CONCLUSION: Surgical inflammation associated with cataract surgery caused a significant increase of macular thickness in control and DR eyes that were not treated with intravitreous bevacizumab. Such macular changes were not accompanied by subfoveal choroidal thickness changes in any of the study groups, suggesting that the changes in macular thickness associated with the surgery are not related to changes in choroidal thickness and that there is no relation between inner blood-retinal barrier status and diabetic choroidal angiopathy.

Switch from intravitreal ranibizumab to bevacizumab for the treatment of neovascular age-related macular degeneration: clinical comparison.

OBJECTIVE: To compare outcomes after switching from intravitreal ranibizumab to bevacizumab in neovascular age-related macular degeneration (AMD). METHODS: A retrospective review of 110 eyes treated in a 1+PRN (pro re nata) clinical setting with ranibizumab that were switched to bevacizumab. Patients analyzed had at least 3 ranibizumab injections followed by at least 3 bevacizumab injections. Changes in best-corrected visual acuity (BCVA), retinal thickness and frequency of injections were compared. RESULTS: The mean duration of ranibizumab treatment was 18.1 months, followed by 12.2 months of bevacizumab. Mean injection rates per month were similar (0.54 and 0.56 respectively, p = 0.230). There were no significant differences between BCVA at baseline and at the time of the switch (52.4 and 54.8 letters, p = 0.059). After the switch, there was a statistically significant decrease in BCVA to 51.7 letters (p < 0.001). CONCLUSION: Switching patients to bevacizumab may have a minor negative effect on the initial gain obtained with ranibizumab; however the degenerative history of wet AMD could explain this small variation in visual acuity.

Anti-VEGF therapy in myopic choroidal neovascularization: long-term results.

PURPOSE: To evaluate the medium- and long-term efficacy of anti-VEGF agents in the treatment of choroidal neovascularization secondary to pathologic myopia (mCNV). METHODS: We performed a retrospective analysis of patients with mCNV who had been treated with intravitreous anti-VEGF for at least 2 years. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared before and after the treatment. The number of injections per year was also assessed. RESULTS: The results were analysed at 2 years for 67 eyes, at 3 years for 52 eyes, at 4 years for 28 eyes and at 5 years for 13 eyes. The mean change from baseline BCVA was significant at 2 years (+8.6 letters; p < 0.001) and this gain remained significantly stable for a period of 5 years. The mean CRT showed a significant decrease over time, with a nadir at 2 years (-104.0 µm; p < 0.001). The mean number of injections performed during the first year was 5.2, being lower in subsequent years (p < 0.001). CONCLUSION: In this subset of patients with mCNV, an intravitreous therapy with anti-VEGF agents proved to have effective results over 5 years, with a sustained increase in BCVA.

Choroidal and macular thickness changes induced by cataract surgery.

BACKGROUND: The aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid. METHODS: In 14 eyes from 14 patients, retinal macular thickness, choroidal submacular thickness, and choroidal peripapillary thickness were measured preoperatively and at one week and one month after phacoemulsification using enhanced depth imaging spectral domain optical coherence tomography. Changes in thickness of the different ocular tissues were evaluated. RESULTS: There was a statistically significant increase in mean retinal macular thickness at one month. In horizontal scans, the mean increase was +8.67±6.75 µm (P<0.001), and in vertical scans, the mean increase was +8.80±7.07 µm (P=0.001). However, there were no significant changes in choroidal morphology in the submacular and peripapillary areas one month after surgery. In vertical scans, there was a nonsignificant increase in choroidal thickness (+4.21±20.2 µm; P=0.47) whilst in horizontal scans a nonsignificant decrease was recorded (-9.11±39.59 µm; P=0.41). In peripapillary scans, a nonsignificant increase in mean choroidal thickness was registered (+3.25±11.80 µm; P=0.36). CONCLUSION: Uncomplicated phacoemulsification induces nonpathologic increases in retinal macular thickness probably due to the inflammatory insult of the surgery; however these changes are not accompanied by significant changes in choroidal thickness. In the posterior segment, the morphologic response to the inflammatory insult of phacoemulsification is mainly observed at the retinal level, and seems to be independent of choroidal thickness changes.

A clear cell renal cell carcinoma inhibiting the response to intravitreal antivascular endothelial growth factor therapy in wet age-related macular disease.

PURPOSE: Wet age-related macular degeneration (AMD) is an ocular disorder that can be successfully treated with intravitreal antivascular endothelial growth factor (VEGF) therapy. We report a case of incomplete response to intravitreal therapy associated with a clear cell renal cell carcinoma (ccRCC). METHODS: A 72-year-old male with wet AMD responded poorly to intravitreal bevacizumab and ranibizumab injections. The removal of a ccRCC led to the spontaneous stabilization of the choroidal neovascular lesion. The renal carcinoma was examined for Von Hippel-Lindau (VHL) gene alterations. Immunohistochemical profiling of the hypoxia-inducible factor (HIF) pathway addressing the marker HIF-1α and its downstream targets VEGF, glucose transporter 1 and carbonic anhydrase IX was performed. RESULTS: Genotyping of the ccRCC revealed the presence of a truncating VHL mutation (p.E134fs*25). Immunohistochemistry displayed HIF pathway target activation and VEGF expression in the ccRCC tumour cells. Following tumour removal, the neovascular lesion remained stable for 6 months without any further anti-VEGF therapy. CONCLUSION: The somatic VHL mutation correlates with persistent high levels of HIF-1α pathway targets and VEGF expression in the ccRCC. We postulate that this increased VEGF in the tumour and subsequently in the plasma levels could have caused the incomplete response to intravitreal anti-VEGF therapy. Stabilization of the wet AMD following tumour removal indicates that the angiogenic secreting tumour (ccRCC) abrogates the response to VEGF inhibitor therapy. Thus, in cases of poor response to intravitreal anti-VEGF therapy, systemic evaluation including plasma levels of VEGF and/or systemic screening for VEGF-producing tumours should be considered.

A novel mutation (Cys83Tyr) in the second zinc finger of NR2E3 in enhanced S-cone syndrome.

BACKGROUND: Enhanced S-cone syndrome (ESCS) is an autosomal recessive retinal disorder characterized by an increased number of S-cones over L/M cones and rods. Mutations in the NR2E3 gene, encoding a photoreceptor-specific nuclear receptor, are identified in patients with ESCS. The purpose of this study is to report the ophthalmic features of a 25-year-old Portuguese male with a typical ESCS phenotype and a novel homozygous NR2E3 mutation. METHODS: The patient underwent a detailed ophthalmic examination including fundus photography, fluorescein angiography (FAF), fundus autofluorescence imaging (FAI), and spectral domain optical coherence tomography (SD-OCT). Full-field electroretinography (ERG), S-cone ERG, and multifocal ERG were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction amplification and direct sequencing. RESULTS: The patient had poor visual acuity but good color vision. Funduscopy showed degenerative changes from the vascular arcades to the midperipheral retina. The SD-OCT revealed macular schisis and cystoid changes that had no fluorescein leakage. The posterior pole showed diffusely increased autofluorescence compared with eccentric areas in both eyes. International-standard full-field ERG showed the typical pathognomonic changes associated with ESCS and the short-wavelength flash ERG was simplified, delayed, and similar to the standard photopic flash ERG. Multifocal ERG showed widespread delay and reduction. Genetic analysis revealed a novel homozygous mutation (p.C83Y), which resides in the second zinc finger of the DNA-binding domain. CONCLUSIONS: This homozygous mutation is likely to affect binding to target DNA sites, resulting in a non-functional behavior of NR2E3 protein. It is associated with a typical form of ESCS with a nondetectable rod response and reduced/delayed mfERG responses at all eccentricities.

Ranibizumab treatment for choroidal neovascularization from causes other than age-related macular degeneration and pathological myopia.

AIM: Evaluation of safety and efficacy of intravitreal ranibizumab in the treatment of choroidal neovascularization (CNV) secondary to causes other than age-related macular degeneration (AMD) or pathological myopia (PM). METHODS: Retrospective and multicentric analysis of 21 eyes with CNV. Nine eyes had angioid streaks, 5 inflammatory chorioretinal diseases, 3 central serous chorioretinopathy and 4 idiopathic CNV. Follow-ups lasted ≥3 months. Best-corrected visual acuity (BCVA), ocular coherence tomography (OCT) and fundus examination were assessed monthly. RESULTS: Sixteen eyes (76%) completed 180 days of follow-up. Overall BCVA increased by +9.8 letters with treatment (p = 0.015). Visual acuity improvements ≥15 letters occurred in 43%. A significant reduction in OCT central thickness was observed. No cases of severe visual acuity loss, systemic or ocular side effects were registered. CONCLUSION: Short-term results of intravitreal ranibizumab for CNV unrelated to AMD or PM are encouraging. This treatment may constitute the only option for some of these patients.

Intravitreal bevacizumab for neovascular age-related macular degeneration with or without prior treatment with photodynamic therapy: one-year results.

PURPOSE: The purpose of this study was to elucidate the effect of prior photodynamic therapy (PDT) on the efficacy of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration. METHODS: One hundred and nine eyes of 102 patients with neovascular age-related macular degeneration were evaluated-80 eyes without prior treatment (group 1) and 29 with prior PDT (group 2). Best-corrected visual acuity, ocular coherence tomography, and funduscopy were assessed monthly. Results were evaluated at 1, 3, 6, and 12 months. RESULTS: One hundred and one eyes completed a 12-month evaluation. At 12 months, best-corrected visual acuity increased 5.6 letters with treatment (P = 0.001): +5.7 letters in group 1 and +5.4 in group 2 (P = 0.92). Overall, visual acuity improved > or =15 letters in 22.5% of eyes: 24.0% of naive eyes versus 18.5% with prior PDT (P = 0.56). Best-corrected visual acuity loss > or =15 letters occurred in 6 eyes, 5 with naive lesions. An overall reduction in ocular coherence tomography central retinal thickness was observed at all time points. Mean number of injections per eye per year was 5.6, 6.13 in group 1 versus 4.22 in group 2 (P = 0.01). Two retinal pigment epithelial tears, one subretinal macular hemorrhage, and two strokes occurred in naive lesions. CONCLUSION: The authors showed similar efficacy for intravitreal bevacizumab independently of prior PDT treatment. Eyes with prior PDT needed a statistically significantly lower number of injections to control their lesions.