Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases.

AIMS: To describe results after neoadjuvant proton beam irradiation followed by transscleral resection of large uveal melanoma. METHODS: Retrospective interventional case series, including 106 consecutive patients. Local tumour control, enucleation and metastasis development were assessed with survival curves. Predictors of local recurrence and metastasis were investigated with log-rank testing. RESULTS: Mean follow-up was 3.2 years. Local recurrence occurred in five cases with an estimated risk of 4.2% and 10.4% at 3 and 5 years after treatment, respectively. Enucleation was performed in 10 cases with an estimated risk of 9.2% and 18.4% at 3 and 5 years, respectively. Significant risk factors for local recurrence were not evident. Metastasis was estimated to occur in 28.4% at 3 years and 40.3% at 5 years, correlating with patient's age only (p=0.01). Seventy four patients (69.8%) underwent vitreoretinal surgery for complications after tumour resection. Median visual acuity (VA) was 20/50 at diagnosis and 20/400 in the third year after treatment. VA preservation of 20/200 or better was achieved in 33 patients (31.1%). CONCLUSION: Neoadjuvant proton beam irradiation may help to prevent local recurrence after transscleral resection. Additional vitreoretinal surgery was frequently needed in the presented series. The majority of patients avoided enucleation and functional blindness.

Proton beam radiotherapy of diffuse iris melanoma in 54 patients.

BACKGROUND: Treatment modalities in iris melanoma include excision, plaque radiotherapy, photon or proton beam therapy and enucleation. In extensive tumours and diffuse seeding, radiotherapy remains as an alternative to enucleation. METHODS: This study is a retrospective, consecutive, interventional, single-institutional case series. 54 patients with a diffuse and non-resectable iris melanoma diagnosed from September 1998 to June 2012 were included. A 68-megaelectron volt proton beam was used to treat the anterior segment with a total dose of 4×12.5 cobalt grey equivalent. The cases were evaluated for local tumour control, eye retention, functional outcome and local complications after treatment. RESULTS: During a mean follow-up of 62.7 months (median 54.8 months, range 5.5-159.6 months), local tumour control was achieved in 96.3% of the patients. Cataract and glaucoma were the main complications developing after irradiation in 42.6% and 55.6%, respectively. In 34 of 44 patients (77.3%) who underwent cataract removal, a visual acuity of 20/40 or better following surgery was preserved. Enucleation was performed in three patients. The reason was suspected tumour recurrence in one and glaucoma in two. Hepatic metastasis occurred in one patient. CONCLUSIONS: As an alternative to enucleation, whole anterior segment fractionated proton beam radiotherapy offered excellent local tumour control in diffuse iris melanoma. Given the limited alternatives, the rate of complications appears acceptable and visual function could be preserved in the majority of the patients during follow-up.

Proton beam therapy of parapapillary choroidal melanoma.

PURPOSE: To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy. DESIGN: Clinical case series, retrospective study. METHODS: We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups. RESULTS: The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects. CONCLUSION: Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients.

Cataract formation: a possible complication of intra-arterial chemotherapy for retinoblastoma.

PURPOSE: To delineate and discuss a not yet described possible ocular complication of selective intra-arterial chemotherapy (SIAC) for treatment of retinoblastoma. METHODS: A 23-month-old girl with a large unilateral retinoblastoma was treated with repeated SIAC using 5 mg melphalan between July 2010 and January 2012. Clinical course of tumor and further ocular changes after therapy and histopathologic findings are described. RESULTS: In total, 5 SIAC were performed over a time period of 18 months. After the last SIAC, diffuse dense cataract prevented further funduscopy. In addition, anterior chamber seeding was obvious, leading to the decision to enucleate the eye. Histopathologically, nearly complete regression of the main tumor mass with prominent calcifications, but vital tumor seeding in the vitreous, on the lens surface, on the ciliary body, and in the anterior chamber, was observed. Peculiar vacuolation of the lens epithelial cells, liquefaction of the subepithelial lens fibers, and diffuse small vacuoles within the lens were striking. CONCLUSIONS: Repeated SIAC with melphalan may induce cataract formation, possibly as a toxic effect of the chemotherapeutic to the lens, maybe combined with radiation exposure during fluoroscopy. This ocular complication should be taken into consideration as a limitation of the number of feasible repeated treatments.

Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival.

Hypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors 1α and 2α (HIF1α and HIF2α). A series of 60 uveal melanomas were immunohistochemically assessed for the expression of VEGF and the phosphorylated/activated form of VEGF receptor 2 (pVEGFR2/KDR), after binding to VEGF. The expression of HIF1α, HIF2α and LDH5 was also investigated. Uveal melanomas overexpressing HIF2α (but not that of HIF1α) were significantly associated with high VEGF (P = 0.005), pVEGFR2/KDR (P < 0.0001) and LDH5 (P ≤ 0.0001). High LDH5 was linked with tumor necrosis (P = 0.01) and increased tumor size (P = 0.03). High VEGF was linked with phosphorylated pVEGFR2/KDR receptors. In univariate analysis high pVEGFR2/KDR receptor expression was significantly related with poor prognosis (P = 0.02). It is concluded that HIF2α plays an important role in the progression of uveal melanomas possibly by promoting the autocrine loop VEGF-pVEGFR2/KDR, and by enhancing the expression of LDHA gene, conferring thus a growth advantage. As pVEGFR2/KDR expression was significantly related with poor prognosis, inhibitors of this receptor may improve the clinical outcome of patients with pVEGFR2/KDR overexpressing uveal melanomas.

Intraoperative localization of tantalum markers for proton beam radiation of choroidal melanoma by an opto-electronic navigation system: a novel technique.

PURPOSE: External beam proton radiation therapy has been used since 1975 to treat choroidal melanoma. For tumor location determination during proton radiation treatment, surgical tantalum clips are registered with image data. This report introduces the intraoperative application of an opto-electronic navigation system to determine with high precision the position of the tantalum markers and their spatial relationship to the tumor and anatomical landmarks. The application of the technique in the first 4 patients is described. METHODS AND MATERIALS: A navigated reference base was attached noninvasively to the eye, and a navigated pointer device was used to record the spatial position of the tantalum markers, the tumor, and anatomical landmarks. Measurement accuracy was assessed on ex vivo porcine eye specimen by repetitive recording of the tantalum marker positions. The method was applied intraoperatively on 4 patients undergoing routine tantalum clip surgery. The spatial position information delivered by the navigation system was compared to the geometric data generated by the EYEPLAN software. RESULTS: In the ex vivo experiments, the maximum repetition error was 0.34 mm. For the intraoperative application, the root mean square error of paired-points matching of the marker positions from the navigation system and from the EYEPLAN software was 0.701-1.25 mm. CONCLUSIONS: Navigation systems are a feasible tool for accurate localization of tantalum markers and anatomic landmarks. They can provide additional geometric information, and therefore have the potential to increase the reliability and accuracy of external beam proton radiation therapy for choroidal melanoma.

Endogenous filamentous fungal endophthalmitis--single-centre survey in patients with acute leukaemia or postallogeneic stem cell transplantation and review of the literature.

Endogenous endophthalmitis caused by filamentous fungi has been infrequently described and its prognosis in immunocompromised patients is largely unknown. Patients were identified through a single-centre database containing patients with endophthalmitis. Cases published since 2002 were reviewed. Clinical and treatment features as well as outcomes were analysed. Six patients were identified from the database. Underlying conditions were haematological malignancies (HM) and/or allogeneic haematopoietic stem cell transplantation (HSCT). Three patients underwent vitrectomy. None of the patients survived and the median time from first evidence of endophthalmitis until death was 33 days. The median time from first evidence of an invasive fungal infection to endophthalmitis was only 5 days. Fifty-six patients were identified from the literature. The majority of these patients underwent vitrectomy (27) or enucleation (10) and received intraocular antifungal therapy (28). Only 13 (23%) of 56 patients experienced an improved vision. The survival rate was 52% in all 56 patients but was significantly less in patients with HM or post-HSCT when compared with all others (26% vs. 70%, respectively; P = 0.003). Endogenous endophthalmitis caused by filamentous fungi is frequently associated with a permanent decrease or loss of vision. This type of fungal infection carries a particular poor prognosis in patients with profound immunosuppression, requiring improved treatment strategies.

Autophagy patterns and prognosis in uveal melanomas.

Autophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents. It has been claimed that, under certain conditions, such a process may be associated with tumor progression. In this study, the autophagic activity was investigated in a series of 99 uveal melanomas after immunohistochemical staining for the autophagy-associated proteins MAP1LC3A and BECN1, most commonly known as LC3A and Beclin 1, respectively. These were assessed in parallel with the hypoxia-inducible factor 1α (HIF1A) and its downstream protein lactate dehydrogenase 5 (composed by five LDHA subunits). Increased autophagic reactivity, detected by MAP1LC3A or BECN1, was associated with intense pigmentation and tumor hypoxia. Uveal melanomas with extensive overexpression of BECN1 or those with underexpression of this protein were associated with the worst prognosis, but the former manifested metastases much earlier than the latter; only 58% of patients with extensive BECN1 overexpression were alive at 4 years, compared with 80% of patients with underexpressed patterns. It is concluded that autophagy is commonly upregulated in uveal melanomas, and may be associated with hypoxia and intense pigmentation. There is a strong association between extensive BECN1 overexpression and early metastases/poor prognosis, and between underexpression of this protein and late metastases/better prognosis.

Results and complications after implantation of a black iris-lens diaphragm in patients with traumatically induced aphakia and aniridia.

PURPOSE: The black iris-lens diaphragm (ILD) can be used in the treatment of traumatic aniridia and aphakia. The aim of our study was to show postoperative functional and anatomic results and complications in a small case series. METHODS: We retrospectively analyzed the files of 16 patients managed with a black ILD or a sole iris diaphragm in the period 1994-2007. Four of them were female and 12 were male. The mean age of the group was 50±17 years. At the time of the implantation, all of the eyes had already undergone primary surgical repair. RESULTS: The preoperative best-corrected visual acuity in half of the patients was =0.1 and remained stable after the first postoperative year. During the follow-up years, one eye developed a subluxation of the implant and one eye an anterior chamber hemorrhage. At the same time, out of 8 eyes carrying a silicone tamponade in the vitreous cavity, silicone oil entered the anterior chamber in 3 cases. In one case, enucleation was undertaken due to phthisis. CONCLUSIONS: In the case of severely traumatized eyes with aniridia and aphakia, the implantation of a black ILD can have a positive effect on functional and anatomic stabilization.

Transarterial chemoembolization of liver metastases from uveal melanoma after failure of systemic therapy: toxicity and outcome.

The liver is the predominant site of metastases in the majority of patients with uveal melanoma, suggesting the evaluation of regional treatment approaches. Here we report our experience with transarterial chemoembolization (TACE) in uveal melanoma patients with pretreated liver metastases. Twenty-five patients were treated with fotemustine-based or cisplatin-based TACE after treatment failure of systemic therapy between 2003 and 2008 at our institution. Grade III toxicity consisted of gastric ulcer (n=1), fever (n=3), splenic infarction (n=1), and thrombocytopenia (n=1). No grade IV toxicity or catheter-associated complications were observed. Fourteen of 25 patients (56%) had stable disease for at least 2 months and four had partial remission. The median progression-free survival (PFS) was 3 months (95% confidence interval: 2-4 months) and the median overall survival (OS) was 6 months (95% confidence interval: 5-7 months), with 15% of patients alive at 1 year. Both PFS and OS were significantly longer, when pretreatment lactate dehydrogenase was below the two-fold upper limit of normal (n=11): PFS 5 versus 2 months (P<0.001) and OS 11 versus 5 months (P=0.012). All patients with lactate dehydrogenase less than 2xupper limit of normal had a clinically detectable benefit. TACE is well tolerated and effective in pretreated patients with liver metastases from uveal melanoma. TACE should further be evaluated as first-line therapy in prospective randomized clinical trials.

Ten-year results of transscleral resection of large uveal melanomas: local tumour control and metastatic rate.

AIMS: To describe the long-term tumour control and metastatic rate after transscleral resection (TSR) of large uveal melanomas in a single-centre study. METHODS: The sample included 210 patients with large uveal melanomas. Univariate analysis of local tumour control and metastatic risk by Kaplan-Meier survival curves and log-rank testing. Cox proportional HR analysis with forward and backward selection was used to identify independent prognostic factors in patients submitted to TSR of a large uveal melanoma. RESULTS: A residual tumour was diagnosed in 6% of the patients. The 5- and 10-year local tumour recurrence rates were 24% and 32%, respectively. Older age, a large basal tumour diameter, the lack of adjuvant ruthenium brachytherapy and retinal detachment led to a 2.6, 2.4, 4.4 and 7.8 times higher risk of melanoma recurrence, respectively. The 5- and 10-year metastatic rates were 28% and 44%, respectively, and were statistical significantly affected by extraocular spread, tumour thickness and local tumour recurrence. CONCLUSIONS: TSR is an alternative to enucleation for the treatment of large uveal melanomas. Results should improve with better patient selection and more effective methods of adjuvant radiotherapy.

Incidence and outcome of endophthalmitis over a 13-year period.

OBJECTIVE: The aim of the study was to assess the functional results and long-term visual prognosis in patients treated for acute endophthalmitis (AE). DESIGN: Observational clinical series. PARTICIPANTS: Evaluation of 120 eyes of 114 patients with AE treated between 1991 and 2004. METHODS: This retrospective institutional analysis included 120 eyes of 114 patients (52 male, 68 female) with AE and a minimum follow-up of half a year. The patients had a mean follow-up of 23 months (6-135 months) and a mean age of 61 years (8 months-94 years) at the time of treatment. Treatment included intraocular injection of antibiotics alone (n = 18, 15%) and vitrectomy combined with intraocular and topical postoperative antibiotics (n = 85, 70%). RESULTS: The most frequent complications were vitreous or retinal hemorrhages (n = 17, 14%), retinal detachment (n = 17, 14%), choroidal detachment (n = 3, 3%), secondary glaucoma (n = 7, 6%), and recurrent endophthalmitis (n = 3, 3%). Four eyes had to be enucleated because of recurrent and uncontrollable infection. Positive microbiological results were achieved in 67 of 88 specimens (76%). The most common isolate was Staphylococcus. At the end of follow-up, visual acuity was reduced (more than 2 lines) in 18 eyes (15%), stable in 22 (18%), and improved (more than 2 lines) in 72 eyes (60%). CONCLUSIONS: AE is a rare but severe disease with a potentially deleterious outcome in affected eyes. In our series, 78% of all eyes had stable or improved postoperative visual acuity following various treatment regimens, depending on the severity of each case.

Ocular involvement in Adamantiades-Behçet's disease in Berlin, Germany.

BACKGROUND: Epidemiological studies demonstrate a prevalence of Adamantiades-Behçet's disease (ABD) in the range of 0.12-420 per 100,000 inhabitants, with the highest rates in Istanbul, Turkey, and the lowest rates in the USA. Ophthalmological data on the prevalence of ocular involvement are limited for ABD in Germany, because most epidemiological studies are based on rheumatological or dermatological data. Berlin is the city with the highest number of non-native German inhabitants, and its multi-ethnic character renders it uniquely appropriate for epidemiological studies on ABD. METHODS: We retrospectively analyzed all ABD patients seen in our department since 1982. All patients fulfilled the criteria of the International Study Group for Behçet's Disease. We found 140 patients (63 female, 77 male), with a mean follow-up of 6.4 years (0.5-22 years). RESULTS: The mean age was 23 at the first manifestation and 32 when the full-blown disease was noted. The mean age at onset of ocular involvement was 30. Most of the patients were of Turkish (n = 73) or German (n = 34) origin. Fifty-six percent developed ocular involvement, which was the first manifestation in 8.6% and the second manifestation in 19.3% of cases. CONCLUSIONS: More than half the patients developed ocular involvement. The calculated prevalence of ocular involvement in ABD is 1.77/100,000 inhabitants for the municipality of Berlin.

Implantation of scleral fixated sutured posterior chamber lenses: a retrospective analysis of 119 cases.

BACKGROUND: The implantation of scleral fixated sutured posterior chamber lenses enables lens implantation in the absence of adequate lens capsule support. Anterior chamber lenses and their side effects can also be avoided, particularly in cases of unilateral aphakia and contact lens incompatibility. METHODS: This study is a retrospective analysis of 119 scleral fixated sutured posterior chamber lenses implanted in 115 patients. Seventy-nine cases of damaged zonula or damaged lens capsule and 17 cases of corneal decompensation secondary to anterior chamber lenses were the main indications for the suture fixation. The mean follow-up was 23 months (6-83 months). RESULTS: In 50% of all cases, improved visual acuity was achieved. Twenty-four percent of patients showed unchanged visual acuity, while 26% had poorer vision postoperatively, mainly because of corneal decompensation following anterior chamber lens explantation. The main postoperative complication was transient rise of intraocular pressure, occurring in 44% of the cases. CONCLUSIONS: In most cases improved or comparable postoperative visual acuity was achieved. The main complication observed was postoperative glaucoma, especially in patients with pre-existing glaucoma.

Retinal detachment after phacoemulsification in high myopia: analysis of 2356 cases.

PURPOSE: To determine the incidence of and risk factors for rhegmatogenous retinal detachment (RD) in highly myopic eyes after cataract surgery. SETTING: Two ophthalmology centers in Munich and Ahaus, Germany. METHODS: This retrospective medical chart review comprised 1519 consecutive patients (2356 eyes) with an axial length (AL) greater than 27.0 mm who had planned phacoemulsification and intraocular lens implantation in the capsular bag. In addition, all patients and/or the referring ophthalmologist were contacted regarding the occurrence of RD and laser capsulotomy and the date of occurrence. RESULTS: Follow-up was longer than 24 months in 84% of eyes. Because some cases of RD were questionably related to the preceding cataract surgery, the absolute incidence of postoperative RD was determined as highest (2.2%) and lowest (1.5%). Sex, history of laser capsulotomy, and increasing AL had no statistically significant effect on the rate of RD. The risk for postoperative RD was significantly higher in eyes of younger patients and eyes with preoperative prophylactic treatment for retinal degeneration. CONCLUSIONS: The risk for postoperative RD in this study (1.5% to 2.2%) corresponds to the incidence of pseudophakic RD and idiopathic RD in myopia described in the literature. The risk profile for postoperative RD in this series cannot be distinguished from the risk profile for idiopathic RD in myopia of this extent. The true effect of prophylactic treatment of degenerative lesions remains to be elucidated.

Longterm visual prognosis of patients with ocular Adamantiades-Behçet's disease treated with interferon-alpha-2a.

OBJECTIVE: Relapsing ocular involvement is one of the major manifestations in Adamantiades-Behçet's disease (ABD). Combining systemic corticosteroids with cyclosporin A is currently the treatment of choice. Interferon-alpha (IFN-alpha) has proven to be effective in mucocutaneous ABD and has been reported to improve ocular lesions. We examined the longterm effects of IFN-alpha-2a in a case series of 45 patients with ocular involvement. METHODS: Since 1988, 45 patients (79 eyes of 90 eyes) with ocular involvement in ABD have been treated with IFN-alpha (3 x 6-9 Mio IU per wk). In the initial acute phase of the disease, patients additionally received short-term corticosteroids (oral prednisolone 100 mg/day), tapered to a maintenance dose of 10 mg/day within 2 weeks. IFN-alpha-2a was administered as longterm therapy with a mean duration of 30 months (range 1.1-101 mo). RESULTS: IFN-alpha-2a/prednisolone treatment was effective against vasculitis, optic nerve neuropathy, and iritis. Sixty-four eyes had no recurrence under therapy. To date, recurrences have been seen in 26 eyes under IFN-alpha treatment. Flu-like symptoms were recorded in nearly all patients (n = 43). Further side effects were dose-dependent reversible thrombocytopenia (n = 1), psychosis (n = 3), depression (n = 13), thyroiditis (n = 1), and reversible diffuse alopecia (n = 7). In our series, 92% of all eyes showed stable or improved visual acuity in longterm followup. CONCLUSION: Longterm remission of ocular inflammation can be achieved with the combination of IFN-alpha and low-dose corticosteroids.

Incidence and clinical characteristics of symptomatic choroidal metastasis from lung cancer.

PURPOSE: To determine the clinical characteristics of symptomatic choroidal metastasis (CM) resulting from metastatic lung cancer. METHODS: Twenty-two consecutive patients with symptomatic CM resulting from lung cancer were retrospectively reviewed for ocular findings, medical history and systemic disease. All patients underwent a complete screening for further organ metastasis by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was determined and compared with the incidence predicted from ocular screening studies. RESULTS: In eight of 22 (36%; 95% confidence interval [CI] 17-59) patients, lung cancer had been diagnosed before occurrence of CM, with a median interval of 13 months. In 14 patients lung cancer was detected after diagnosis of CM, with a median interval of 1 month. Choroidal metastasis was unilateral, solitary and located close to or at the posterior pole in the majority of patients. Further organ metastasis with a median number of three affected organ systems was present in 19 (86%; 95% CI 65-97) patients. Median survival after diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung cancer patients with CM identified in an ocular screening study. The mean number of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was two orders of magnitude less than predicted from screening studies. CONCLUSIONS: Symptomatic choroidal lung cancer metastasis in the majority of patients presents as a solitary tumour before diagnosis of lung cancer in patients with multiple organ systems affected by metastatic disease. Contrary to predictions from ocular screening studies, it is a rare clinical entity.

ERG variability in X-linked congenital retinoschisis patients with mutations in the RS1 gene and the diagnostic importance of fundus autofluorescence and OCT.

PURPOSE: X-linked congenital retinoschisis (RS) is a relatively frequent retinal dystrophy associated with RS1 gene mutations. A negative electroretinogram (ERG), i.e., a b/a wave ratio <1.0 in the standard combined response, is considered a key diagnostic feature of RS. Only a few cases without a negative ERG have been reported. METHODS: This study includes 24 RS patients with RS1 mutations. ERGs (according to ISCEV standards, n = 23), ON-OFF-responses (n = 9), fundus autofluorescence (FAF, n = 8), and optical coherence tomography (OCT, n = 6) were performed. RESULTS: The mean age at examination was 22.6 years (0.5-53.2 years), and median visual acuity was 0.3 (no light perception to 0.6). A negative ERG was found in 13 of 23 patients (56.5%), of whom one patient presented a negative ERG at the 2-year follow-up, with an initial b/a wave ratio >1.0. Another patient had a b/a wave ratio of 0.96 in one eye and 1.02 in the fellow eye. In 10 of 23 patients, the b/a wave ratio ranged from 1.03 to 1.34. Single-flash cone and 30 Hz flicker responses were always reduced. FAF and OCT were pathologic in all patients tested. FAF was increased in the fovea. OCT revealed foveal schisis to various degrees and thinning of the retina in an older patient. CONCLUSIONS: Although ERG abnormalities were detected in all patients tested, more than 40% of patients with RS1 mutations did not have a negative ERG. In clinically suspected RS a combination of ERG, FAF, OCT, and molecular-genetic testing is advised to verify the diagnosis.