Relationship between Aflibercept Efficacy and Genetic Variants of Genes Associated with Neovascular Age-Related Macular Degeneration: The BIOIMAGE Trial.

PURPOSE: To identify the genetic variants of the vascular endothelial growth factor (VEGF) pathway genes and other genes associated with neovascular age-related macular degeneration (nAMD) as possible predictive biomarkers of a favorable treatment response to aflibercept. DESIGN: A 52-week (with extension phase: 104-week), prospective, open-label, single-arm, multicenter, phase IV trial was conducted in Spain. PARTICIPANTS: Patients with nAMD were enrolled. METHODS: Aflibercept was administered every 8 weeks until week 48 (after 1-monthly loading doses over 3 months). After week 48, the interval between visits for aflibercept administration was extended by 2 weeks per visit to a maximum of 12 weeks if no evidence of disease activity was observed. A total of 338 SNPs in 90 genes associated with nAMD were analyzed. MAIN OUTCOME MEASURES: Efficacy was evaluated mainly with best-corrected visual acuity (BCVA), and adverse events (AEs) were reported. Treatment efficacy was defined as an increase in BCVA ≥15 letters versus the baseline visit. Univariate and multivariate logistic regressions were used to associate single-nucleotide polymorphisms (SNPs) and treatment efficacy. RESULTS: 194 nonconsecutive patients were enrolled, 170 completed the 52-week follow-up, and of the 85 patients who started the extension phase, 77 completed this phase. Mean BCVA increased from baseline to weeks 52 and 104 by 9 and 10 letters (p = 0.0001 for both), respectively. The percentages of patients gaining ≥15 letters in weeks 52 and 104 were 33 and 31%, respectively. Multivariate logistic regression showed significant associations of 6 SNPs (in 6 genes) with treatment efficacy: rs12366035 (VEGFB; TT; odds ratio [OR] 217), rs25681 (C5; AA/AG; OR 19.7/8.3), rs17793056 (CX3CR1; CT/CC; OR 8.1/6.2), rs1800775 (CETP; CC; OR 6.6), rs2069845 (IL6; GG/AA; OR 5.6/3.3), and rs13900 (CCL2; CT; OR 4.0). One percent of the patients reported arteriothrombolic events related to aflibercept (cerebrovascular accident) according to the Antiplatelet Trialist Collaboration, and 2% reported serious ocular (retinal pigment epithelial tear, retinal tear, and endophthalmitis) and systemic (cardiac failure, hypersensitivity, and transient ischemic attack) AEs related to aflibercept. CONCLUSIONS: Results suggest strong pharmacogenetic associations between one genetic variant of VEGFB (TT, rs12366035) and C5 (AA, rs12366035) genes and the BCVA response after 52-week aflibercept treatment in patients with nAMD. Likewise, the results support the efficacy of aflibercept observed in phase III studies and a good safety profile.

Identification of a novel homozygous ARSG mutation as the second cause of Usher syndrome type 4.

PURPOSE: Usher syndrome is a genetic disease characterized by combined sensorineural hearing loss, retinitis pigmentosa, and vestibular areflexia, with 15 known causative genes. Depending on the severity and onset of the symptoms, 3 different subtypes of the pathology have been classically established, although an increasing number of rare cases are being accumulated as atypical forms. The present work aims to discover the genetic cause in a patient with atypical Usher syndrome, by performing whole exome sequencing in several family members. OBSERVATIONS: The obtained results identified a novel homozygous missense mutation (p.Asp44Asn) in the ARSG gene as the cause of the disease, which was characterized by late-onset progressive symptoms in the patient. A resembling phenotype, recently defined as the novel Usher syndrome type 4, was described in three families sharing another ARSG mutation. Both mutations affect two contiguous amino acid residues, which appear to be critical for the correct function of the protein. CONCLUSIONS AND IMPORTANCE: These findings support the identification of the second disease mutation in this gene and a new evidence of the implication of ARSG in the genetic basis of Usher syndrome type 4.

Characterization of the cone-rod dystrophy retinal phenotype caused by novel homozygous DRAM2 mutations.

Cone-rod dystrophies (CRD) are a group of Inherited Retinal Dystrophies (IRD) characterized by the primary involvement of cone photoreceptors, resulting in the degeneration of the central retina, or macula. Although there are more than 55 CRD genes, a considerable percentage of cases remain unsolved. In this context, the present study aimed to describe and characterize the phenoptype and the genetic cause of 3 CRD families from a cohort of IRD cases. Clinical evaluation in each patient was supported by a complete ophthalmological examination, including visual acuity measurement, fundus retinography, fundus autofluorescence imaging, optical coherence tomography and full-field electroretinography. Molecular diagnoses were performed by whole exome sequencing analyzing a group of 279 IRD genes, and cosegregation of the identified pathogenic variants was confirmed by Sanger sequencing. Three novel homozygous mutations in the autophagy gene DRAM2 were identified as the molecular cause of disease in the three families: c.518-1G>A, c.628_629insAG and c.693+2T>A. Clinical data revealed that the 3 patients presented a shared CRD phenotype with adult-onset macular involvement and later peripheral degeneration, although the age of onset, evolution and severity were variable. In order to characterize the transcription effects of these variants, mRNA expression studies were performed. The results showed alterations in the DRAM2 transcription, including alternative splicing forms and lower levels of mRNA, which correlated with the phenotypic variability observed between patients. For instance, frameshift mutations were related to a less severe phenotype, with circumscribed mid-peripheral involvement, and lower levels of mRNA, suggesting an activation of the nonsense-mediated decay (NMD) pathway; while a more severe and widespread retinal degeneration was associated to the inframe alternative splicing variant reported, possibly due to a malfunctioning or toxicity of the resulting protein. Following these findings, DRAM2 expression was assessed in several human tissues by semi-quantitative RT-PCR and two isoforms were detected ubiquitously, yet with a singular tissue-specific pattern in retina and brain. Altogether, although the unique retinal phenotype described did not correlate with the ubiquitous expression, the retinal-specific expression and the essential role of autophagy in the photoreceptor survival could be key arguments to explain this particular DRAM2 phenotype.

Establishment of an induced pluripotent stem cell line (FRIMOi005-A) derived from a retinitis pigmentosa patient carrying a dominant mutation in RHO gene.

Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by the progressive degeneration of photoreceptors. In the present study, we have generated an induced pluripotent stem cell (iPSC) line derived from a RP patient with a dominant mutation in the RHO gene, responsible for the synthesis of rhodopsin. The reprogramming of these iPSCs was performed from skin fibroblasts by the Sendai-virus based approach. Characterization of the iPSC line showed a normal karyotype carrying the RHO mutation, expressed pluripotency markers and could be differentiated to endoderm, mesoderm and ectoderm in vitro.

Generation of two iPS cell lines (FRIMOi003-A and FRIMOi004-A) derived from Stargardt patients carrying ABCA4 compound heterozygous mutations.

Recessive Stargardt disease (STGD1) is an autosomal recessive retinal dystrophy, caused by mutations in the retina-specific ATP-binding cassette transporter (ABCA4) gene, which plays a role as a retinaldehyde flippase in the photoreceptor outer segments. In this work, two human induced pluripotent stem cell (iPSC) lines were generated from STGD1 patients carrying compound heterozygous mutations in ABCA4. Skin fibroblasts were reprogrammed with the Yamanaka factors using a non-integrating, Sendai virus-based approach. Both iPSC lines displayed typical embryonic stem cell morphology, had normal karyotype, expressed several pluripotency markers and were able to differentiate into all three germ layers. Resource table.

Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies.

Inherited retinal dystrophies (IRD) comprise a wide group of clinically and genetically complex diseases that progressively affect the retina. Over recent years, the development of next-generation sequencing (NGS) methods has transformed our ability to diagnose heterogeneous diseases. In this work, we have evaluated the implementation of whole exome sequencing (WES) for the molecular diagnosis of IRD. Using Ion ProtonTM system, we simultaneously analyzed 212 genes that are responsible for more than 25 syndromic and non-syndromic IRD. This approach was used to evaluate 59 unrelated families, with the pathogenic variant(s) successfully identified in 71.18% of cases. Interestingly, the mutation detection rate varied substantially depending on the IRD subtype. Overall, we found 63 different mutations (21 novel) in 29 distinct genes, and performed in vivo functional studies to determine the deleterious impact of variants identified in MERTK, CDH23, and RPGRIP1. In addition, we provide evidences that support CDHR1 as a gene responsible for autosomal recessive retinitis pigmentosa with early macular affectation, and present data regarding the disease mechanism of this gene. Altogether, these results demonstrate that targeted WES of all IRD genes is a reliable, hypothesis-free approach, and a cost- and time-effective strategy for the routine genetic diagnosis of retinal dystrophies.

MACULAR BUCKLING WITH ANDO PLOMBE MAY INCREASE CHOROIDAL THICKNESS AND MIMIC SEROUS RETINAL DETACHMENT SEEN IN THE TILTED DISK SYNDROME.

PURPOSE: Serous subfoveal detachment has been described in the literature as a complication that appears at the border of the staphyloma. Macular buckling induces a postoperative inward bulge that resembles the ridge of a staphyloma. We describe three patients who developed a serous subfoveal detachment after uneventful macular buckling. To our knowledge, this complication, that shares similarities with the staphyloma ridge detachment, has not been previously reported. METHODS: The clinical records of all cases that underwent macular buckling at our clinic were reviewed. RESULTS: Three patients developed a serous subfoveal detachment that could not be explained by choroidal neovascularization or polypoidal vascular choroidopathy. Along with the development of the subfoveal detachment, we observed an increase of the choroidal thickness beneath the fovea. This thickening, that tended to progress during the follow-up, resolved spontaneously after explantation of the buckle. The decrease in foveal thickness did also lead to resolution of the subfoveal detachment. CONCLUSION: The development of the subfoveal detachment in our patients was closely associated with a focal increase of the choroidal thickness after the macular buckling. After the buckle was removed, the choroidal thickness went back to the normal prebuckling values and the detachment resolved in all three patients. This leads us to think that there is a close association between choroidal thickness and the serous subfoveal detachment.

Effect of intravitreal injection of dexamethasone 0.7 mg (Ozurdex®) on intraocular pressure in patients with macular edema.

BACKGROUND: To evaluate the effect of Ozurdex® on intraocular pressure in patients with macular edema alone (group 1) or associated with glaucoma or ocular hypertension (group 2). METHODS: A clinical, retrospective, observational, comparative study included 92 eyes with macular edema treated with a single injection of Ozurdex®; 27 eyes were previously diagnosed with glaucoma or ocular hypertension. RESULTS: The mean intraocular pressure (group 1 vs. group 2) after injection was 12.1 versus 19.9 mm Hg, (p < 0.05; day 1); 17.5 versus 19.7 mm Hg (p < 0.05; month 1); 18.4 versus 20.9 mm Hg (p < 0.05; month 2); 15 versus 17.4 mm Hg (p < 0.05; month 3); 13.9 versus 16.7 mm Hg (p > 0.05; month 6); 13.8 versus 15.1 mm Hg (p > 0.05; month 9) and 13.1 versus 16.4 mm Hg (p > 0.05; month 12). Thirty eyes (32.6%) showed ocular hypertension (intraocular pressure >21 mm Hg) after the injection: 21.5% of group 1 and 59.3% of group 2. In group 2, 27 eyes (100%) needed medical treatment to reduce intraocular pressure in comparison to 8 patients (12.3%) in group 1 (p < 0.001). CONCLUSIONS: Intravitreal injection of Ozurdex® was associated with ocular hypertension in 32.6% of the eyes. Previous glaucoma or ocular hypertension are risk factors for this increase.

Myopic traction maculopathy.

Myopic traction maculopathy is a high myopia-related complication caused by several mechanisms with traction as a common pathway. Macular hole-related retinal detachment is considered to be the final stage of progressive foveoschisis. In this setting, release of all vitreous and epiretinal tractions is essential in order to achieve surgical success. Pars plana vitrectomy has proven useful in the treatment of myopic foveoschisis, with both good visual and anatomical results. However, the surgical technique for the treatment of macular hole-related retinal detachment is still a controversial issue: reoperations are common and the final visual prognosis is limited, especially in those cases with a pronounced posterior staphyloma. We must also bear in mind that a highly myopic eye has some characteristic traits that may complicate vitreoretinal surgery. In these cases, microincision vitrectomy surgery may offer some advantages compared to conventional vitrectomy.

Visual and anatomical outcome after macular buckling for macular hole with associated foveoschisis in highly myopic eyes.

BACKGROUND: Macular hole (MH) with associated foveoschisis is very specific to highly myopic eyes with a pronounced posterior staphyloma. A high axial length increases the risk of foveoschisis, MH formation and retinal detachment secondary to a macular hole (MHRD). These highly myopic MH show poor surgical outcomes after vitrectomy and internal limiting membrane peeling compared with non-myopic MH. The posterior staphyloma seems to play an important role, and thus macular buckling could prove useful to improve both visual and anatomical results. METHODS: Sixteen highly myopic eyes with MH and associated foveoschisis that underwent macular buckling were studied. Vitrectomy combined with macular buckling was performed in all 16 eyes. Optical coherence tomography was performed to confirm MH closure in all cases. RESULTS: Combined vitrectomy and macular buckling resulted in MH closure in all patients. Best-corrected visual acuity (BCVA) improved in 13 out of 16 eyes (81.25%), remained stable in 2 eyes (12.5%) and worsened in 1 eye (6.25%). Mean preoperative BCVA was 20/125, whereas mean postoperative BCVA was 20/50. CONCLUSIONS: Combined vitrectomy and macular buckling is a safe and effective approach to achieve primary closure of MH in eyes with posterior staphyloma and associated foveoschisis. Eyes with a high axial length show a less favourable prognosis, which can be partially overcome by means of macular buckling.

Macular buckling for previously untreated and recurrent retinal detachment due to high myopic macular hole: a 12-month comparative study.

PURPOSE: To evaluate postoperative outcomes after macular buckling together with pars plana vitrectomy (PPV) in previously untreated and recurrent retinal detachment secondary to macular hole (MH) in highly myopic eyes. METHODS: In a retrospective cohort study, 42 eyes of 42 high myopic patients with retinal detachment due to MH were evaluated. Patients were divided into previously untreated retinal detachment (group 1, 21 eyes) and recurrent retinal detachment (group 2, 21 eyes). Macular buckling and PPV were performed in all patients. Main outcomes included retinal reattachment rate, macular hole closure rate and best-corrected visual acuity (BCVA) at 3, 6, and 12 months. Optical coherence tomography (OCT) was performed both pre- and postoperatively in all patients to assess the anatomical status of the macula. RESULTS: Primary retinal reattachment rate in group 1 was 95% (20/21), which increased to 100% (21/21) after a second surgery. MH closure was achieved in 81% of patients (17/21) after one surgery. The mean preoperative BCVA (logarithm of the minimum angle of resolution, LogMAR) improved from 1.32 (95% CI 1.19;1.44) to 0.76 (95% CI 0.56;0.96) 12 months postoperatively. In all except one case, gas tamponade was preferred. Primary reattachment and MH closure rate in group 2 were 90.5% (19/21) and 57% (12/21) respectively, and did not improve after a second surgery. Preoperative BCVA (LogMAR) was 1.39 (95% CI 1.29;1.49) and improved to 0.95 (95% CI 0.75;1.15) at 12 months. Silicone oil tamponade was used in seven of 21 patients, and finally was removed in five of them. CONCLUSIONS: Macular buckling combined with PPV should be considered a preferred surgical approach both in primary and recurrent retinal detachment secondary to MH in high myopic eyes. Nevertheless, visual outcomes seem to be better when macular buckling is chosen as first-line treatment.

Scleral fixation of dexamethasone intravitreal implant (OZURDEX®) in a case of angle-supported lens implantation.

OZURDEX(®) is a biodegradable drug delivery system which has been reported to be an effective treatment in cases of macular edema. However, migration of the implant into the anterior chamber with elevation of intraocular pressure and corneal decompensation might occur in some cases. We report a case of an 80-year-old male who underwent intravitreal scleral fixation of OZURDEX(®) due to postoperative macular edema secondary to complicated cataract surgery. He had a previous angle-supported lens implantation with superior Nd:YAG laser iridotomy. During surgery, the dexamethasone implant was introduced into the vitreous cavity and sutured to the sclera using a 10-0 non-absorbable polypropylene suture to prevent the risk of anterior complications in case of migration into the anterior chamber. After 6 months of follow-up, the macular edema had disappeared completely, the drug delivery system was not observed in the posterior segment and best-corrected visual acuity improved from 20/125 to 20/40 (Snellen equivalent). Neither anterior nor posterior segment complications were reported during the follow-up period. Intravitreal scleral fixation of the OZURDEX(®) to the pars plana could be recommended as an alternative technique to avoid anterior migration of the device in a patient with an anterior chamber intraocular lens, which may lead to corneal decompensation and increased intraocular pressure.

Assessment of OCT measurements as prognostic factors in myopic macular hole surgery without foveoschisis.

BACKGROUND: To assess the role of Spectral Domain Optical Coherence Tomography (SD-OCT) measurements as prognostic factors in myopic macular hole (MMH) surgery. METHODS: In a retrospective cohort study, we evaluated 42 eyes of 42 patients (Spherical equivalent > -6.00 D) who underwent pars plana vitrectomy with internal limiting membrane peeling for MMH without foveoschisis. Statistical analysis was performed to correlate postoperative best corrected visual acuity (BCVA) with preoperative BCVA, age, degree of myopia and seven preoperative OCT measurements: macular hole (MH) base, MH minimum diameter, MH height, Hole Form Factor (HFF), Macular Hole Index (MHI), Diameter Hole Index (DHI) and Tractional Hole Index (THI). RESULTS: Primary and final anatomical success rate were 83.3% (35/42) and 90.5% (38/42), respectively. Four patients deferred reoperation and three underwent a second surgical approach to achieve MH closure. A posterior staphyloma was observed in 27 of 42 patients, and in three of them the MH was located in the apex of the staphyloma. Two of these three cases showed an open MH after the first surgery. Postoperative visual acuity improved in 22/42 (52.4%) patients, worsened in 7/42 (16.7%) and remained unchanged in 13/42 (30.9%). Only MH minimum diameter (P = 0.03) and HFF (P = 0.02) correlated significantly with postoperative BCVA. CONCLUSIONS: Minimum diameter and HFF are strongly correlated with postoperative visual outcomes in cases of MMH. Since analyzing MH configuration seems to improve the anatomical success rate after vitreous surgery in highly myopic patients, these parameters should be preoperatively evaluated by SD-OCT.

Surgical outcomes of macular buckling techniques for macular retinoschisis in highly myopic eyes.

PURPOSE: To report the anatomic and visual results following macular buckling for patients with macular retinoschisis related to high myopia. METHODS: Thirty-nine highly myopic eyes (mean refractive error -16.7 D; range, -9 to -24 D) of 36 patients (mean age 59 years; range, 35-79 years) presenting with macular retinoschisis associated with a posterior staphyloma, who underwent combined vitrectomy and macular buckling were evaluated. Main outcome measures included best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) findings. Three cases were excluded due to short follow-up (less than 3 months). The mean follow-up was 16 months. RESULTS: The mean BCVA increased from 0.76 to 0.43 LogMAR (p = 0.001). Visual acuity improved in 30 eyes (83.3%), remained stable in three eyes (8.3%) and decreased in three eyes (8.3%). OCT showed resolution of foveoschisis with foveal reattachment in all eyes. None of the evaluated patients developed a macular hole during follow-up. CONCLUSION: Macular buckling associated with vitrectomy results in good anatomic and visual outcomes in patients with myopic foveoschisis.

Macular buckling for eyes with myopic foveoschisis secondary to posterior staphyloma.

PURPOSE: To determine the effectiveness of macular buckling in eyes with myopic foveoschisis and describe two methods of macular buckling: hard silicone implant and Ando plombe. METHODS: Sixteen eyes of 16 consecutive patients with myopic foveoschisis who underwent surgery with the macular buckling procedure were studied. Pars plana vitrectomy combined with macular buckling with hard silicone implant was used in 6 eyes, whereas the other 10 eyes underwent pars plana vitrectomy and macular buckling with the Ando macular plombe. RESULTS: Macular buckling, with both hard silicone implant and macular plombe resulted in reduction of retinal thickness in all patients. Best-corrected visual acuity improved in 14 of 16 eyes (87.5%), whereas it remained stable or decreased in 2 eyes (12.5%). Mean preoperative best-corrected visual acuity was 20/125 (mean logarithm of the minimal angle of resolution 0.8), whereas mean postoperative best-corrected visual acuity improved to 20/50 (mean logarithm of the minimal angle of resolution 0.39). Both methods showed a similar rate of complications, the most frequent being the development of localized areas of retinal pigment epithelium atrophy. CONCLUSION: Combined pars plana vitrectomy and macular buckling is an effective approach to treat myopic foveoschisis with both anatomical and visual improvement. Despite a similar complication rate with both buckling techniques, macular buckling with the Ando plombe was found to be technically easier with shorter surgical times.

Nonsense-mediated decay as the molecular cause for autosomal recessive bestrophinopathy in two unrelated families.

PURPOSE: To characterize the molecular basis of two novel BEST1 mutations causing autosomal recessive bestrophinopathy (ARB). Strong evidence argues in favor of the dominant negative effects of most autosomal dominantly inherited mutations, whereas there is only weak support for the molecular basis of the ARB phenotype. METHODS: Patients underwent ophthalmic examination, color and autofluorescence fundus imaging, optical coherence tomography (OCT), electrooculogram, and full-field electroretinogram (ERG). BEST1 was directly screened for mutations in two ARB unrelated patients. The pathogenicity of the new BEST1 variants was assessed in silico and in vivo. RESULTS: Two unrelated patients with diagnoses of ARB showed retinal pigment epithelial disturbances and abnormal ERGs. Each patient was homozygous for a novel BEST1 mutation, c.521_522del and c.1100+1G>A. A carrier sibling (WT/c.521_522del) was unaffected. Both mutations generate a frameshift and a premature stop codon that, if translated, would seriously compromise bestrophin-1 function. However, the in vivo quantitative RT-PCR assays showed that most of the mutated transcripts were eliminated before translation because the mRNA-BEST1 levels were dramatically diminished the controls. CONCLUSIONS: In truncating BEST1 mutations, the null phenotype associated with ARB is attributed to a substantial decrease of BEST1 expression promoted by the nonsense-mediated decay (NMD) surveillance mechanism. Moreover, the severity of the phenotype increases with the preserved amount of altered transcript, suggesting that the clinical outcome reflects the combined null and dominant negative effects of the two mutations over the patient's genetic background.

En face optical coherence tomography of inner retinal defects after internal limiting membrane peeling for idiopathic macular hole.

PURPOSE: To describe the appearance of inner retinal defects using en face spectral domain optical coherence tomography (SD-OCT) after idiopathic full-thickness macular hole (FTMH) surgery, referred to as concentric macular dark spots (CMDS). METHODS: In a retrospective cohort study, the authors evaluated 36 eyes of 36 patients with large idiopathic MH (>400 µm) who underwent standard three-port pars plana vitrectomy with internal limiting membrane (ILM) peeling. All patients were analyzed using B-scan and C-scan en face SD-OCT before and after surgery to determinate the OCT pattern of the retinal surface. RESULTS: Mean follow-up was 10 months (±8.45 SD; range, 3-30 months). Three months after surgery 36 of 36 eyes (100%) showed a CMDS appearance on en face SD-OCT images. Anatomic success rate was 100% (36/36 eyes) after a single surgical procedure. Once they were evident, these dark spots observed on the retinal surface were not progressive and remained stable over time. CONCLUSIONS: Inner retinal defects frequently occurred after idiopathic MH surgery when ILM was peeled. To the authors' knowledge, this feature has not been previously reported using an en face SD-OCT imaging, and it consisted of numerous CMDS in the same direction of the optic nerve fibers. All patients in the study showed this typical OCT pattern 3 months after surgery. Thus, the authors suggest that this is a helpful, noninvasive technique to assess complete ILM removal in FTMH surgery if CMDS appearance on the retinal surface is reported.

Radiation maculopathy after epimacular brachytherapy for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To describe a case of radiation maculopathy after a 24-Gy single-fraction epimacular brachytherapy delivered concomitantly with ranibizumab for the treatment of age-related macular degeneration. METHODS: Case report. RESULTS: An 82-year-old man with neovascular age-related macular degeneration was treated with epiretinal brachytherapy and 2 intraocular injections of ranibizumab with initial good response. Nineteen months after initial treatment, visual acuity decreased and the patient was diagnosed of radiation maculopathy. CONCLUSION: Radiation-related ocular side effects such as maculopathy may become evident several years after the treatment. Thus, vascular abnormalities that may appear in the follow-up of these patients can easily be misdiagnosed as a complication of the previous choroidal neovascularization.