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We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level.

To report the clinical and molecular genetic findings in two brothers with retinitis pigmentosa (RP) and mevalonate kinase deficiency (MKD).The brothers were examined clinically and with fundus autofluorescence, near-infrared autofluorescence, and spectral domain optical coherence tomography. Targeted resequencing was done with a custom designed gene panel containing 78 genes associated with RP. Mutations were confirmed by direct Sanger sequencing.Both brothers, aged 46 and 47 years, were found to carry compound heterozygous mutations in the MVK gene (c.59AC, c.1000GA) encoding mevalonate kinase. They presented with severe ataxia, pseudophakia due to early onset cataract, and progressed retinitis pigmentosa. In one brother with cystoid macular edema, treatment with dorzolamide was beneficial. Serum IgD levels were markedly increased in both brothers and mevalonic acid blood and urine levels were markedly increased in the one brother who could be examined. The disease severity differed between the brothers-one had more severe ataxia and less severe visual deficiency compared to the other.MKD can be associated with RP and early onset cataract. Most MKD patients developing RP carry the (p.Ala334Thr) mutation. Macular edema can be treated using local dorzolamide.

Aims To evaluate progression of morphological alterations in chloroquine (CQ) or hydroxychloroquine (HCQ) retinopathy after drug cessation. Methods Eleven female patients (age range at drug cessation 46–78 years; treatment duration 5–20 years) were examined between 2.1 and 7.1 years after drug cessation. In addition to clinical examination, they underwent high-resolution optical coherence tomography (OCT) (spectral domain OCT (SD-OCT); Spectralis OCT, Heidelberg Engineering, Germany), fundus autofluorescence (FAF), near-infrared autofluorescence (NIA; HRA2, Heidelberg Engineering, Germany) and ultra-wide-angle fundus autofluorescence (UW-FAF; Optos 200Tx; Optos PLC, UK). Results Two patients with very limited parafoveal retinopathy did not present with progression within 3 years. In the remaining nine patients, visual acuity deteriorated and progression of retinal degeneration could be documented. FAF, UW-FAF and NIA changes included an increase of affected area or a regional increase or decrease of FAF or NIA intensity. SD-OCT changes included reduction of retinal thickness, an increased area of photoreceptor or retinal pigment epithelial loss, development or increase of cystoid macular oedema (4/9) or development of epiretinal membranes (5/9). Therapy of cystoid macular oedema was of limited benefit. Conclusions CQ retinopathy can progress over a long period of time after drug cessation and may be complicated by cystoid macular oedema, epiretinal membrane formation and peripheral involvement.

Purpose To investigate the advantage of near-infrared autofluorescence (787 nm) for the detection of melanocytic lesions in a patient with bilateral diffuse uveal melanocytic proliferation in association with esophageal carcinoma complicated by most likely unilateral choroidal metastasis. Methods In this retrospective case report, a 55-year-old woman referred for the evaluation of sudden visual loss underwent normal ophthalmological evaluation and, in addition, was examined with near-infrared reflectance, near-infrared autofluorescence, fundus autofluorescence (Heidelberg Retina Angiograph II [HRA2; Heidelberg Engineering]), spectral domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering), and multifocal electroretinography (RetiScan; Roland Consult). Results The patient had been diagnosed with esophageal carcinoma 3 months before the onset of visual symptoms. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Bilateral patchy melanocytic proliferation was detected on ophthalmoscopy. The extent of lesions was best detected with near-infrared reflectance and near-infrared autofluorescence, whereas fundus autofluorescence and spectral domain optical coherence tomography did not reveal alterations of the outer retina or retinal pigment epithelium in this early stage of bilateral diffuse uveal melanocytic proliferation. The right eye showed in addition to the findings on the left eye choroidal folds in the fovea and an elevated lesion inferotemporal of the fovea suspicious of a choroidal metastasis. In the B-scan ultrasonography, a homogenous lesion was seen. Spectral domain optical coherence tomography demonstrated a mild accumulation of subretinal fluid adjacent to and over the choroidal metastasis. Transretinal biopsy of this elevated lesion revealed a low differentiated carcinoma of squamous epithelium, compatible with choroidal metastasis of the esophageal carcinoma. The choroidal metastasis increased within 3 months after the first visit. The visual acuity dropped in both eyes. The patient died 6 months after her first visit. Conclusions Bilateral diffuse uveal melanocytic proliferation can be associated with esophageal carcinoma as a systemic malignancy. Near-infrared imaging can be helpful to detect early stages of BDUMP and can help offer recently reported treatment options at an early stage of disease.

The purpose of this study was to compare near-infrared fundus autofluorescence(NIA, excitation 787 nm, emission800 nm) with fundus autofluorescence (FAF,excitation 488 nm, emission500 nm) in patients with age-related macular degeneration(AMD).Fundus autofluorescence and NIA were obtained using a confocal scanning laser ophthalmoscope (HRA2) in 308 eyes (172 patients) with AMD [age-related maculopathy(n 116), geographic atrophy (n 77), and neovascular AMD (n 115)].Retinal pigment epithelial alterations were detected with FAF and NIA in all eyes and showed a similar lesion size in 81.8%. In age-related maculopathy, spots of increased FAF (87.9%) were more frequent than spots of reduced FAF (26.7%). Spots of increased and reduced NIA were of similar frequency (66.4%). A higher relative intensity of FAF was more frequent (72.4%) than higher relative NIA intensity (16.4%), suggesting that loss of NIA usually precedes loss of FAF. The junctional zone of geographic atrophy presented with increased NIA (19.5%), increased FAF (10.4%), or an increase of both(22.1%). In neovascular AMD, exudative changes were better visualized with FAF (56.5%)compared with NIA (33.9%).Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin in the pathophysiological process and provide further insight into the development of AMD and noninvasive monitoring of future therapeutic interventions.

To compare melanin-related near-infrared fundus autofluorescence (FAF; NIA, excitation 787 nm, emission800 nm) with lipofuscin-related FAF (excitation 488 nm, emission500 nm) in retinitis pigmentosa (RP).Thirty-three consecutive RP patients with different modes of inheritance were diagnosed clinically, with full-field ERG, and if possible with molecular genetic methods. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2).Rings of increased FAF were present within an area of preserved retinal pigment epithelium (RPE) at the posterior pole (31/33). Rings of increased NIA were located in the same region as rings of increased FAF. In contrast to FAF, NIA showed a precipitous decline of NIA peripheral to the ring. In larger areas of preserved NIA (11/31), pericentral and foveal NIA were of similar intensity with an area of lower NIA in between. In smaller areas of preserved NIA (20/31), NIA was homogeneous from the perifovea to the fovea. In one patient without a ring of increased FAF, NIA distribution was normal. In the remaining patient with severely advanced RP, no residual RPE as well as no FAF and NIA were detectable.Characteristic features for FAF and NIA alterations in a heterogeneous group of RP patients indicate a common pathway of RPE degeneration. Patterns of NIA and FAF indicate different pathophysiologic processes involving melanin and lipofuscin. Combined NIA and FAF imaging will provide further insight into the pathogenesis of RP and non-invasive monitoring of future therapeutic interventions.

Purpose To compare melanin-related near-infrared fundus autofluorescence (NIA; excitation 787 nm, emission > 800 nm) to lipofuscin-related fundus autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with retinal dystrophies associated with ABCA4 gene mutations (ABCA4-RD). Design Observational case series. Methods Sixteen consecutive patients with ABCA4-RD diagnosed in one institution were included. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany). The pattern and size of retinal pigment epithelial (RPE) alterations detected with FAF and NIA were evaluated. Results FAF and NIA alterations were detected in all patients. In 7 of 16 patients, the alterations progressed beyond the vascular arcades, and in 9 of 16, they were confined to the macula. Spots of increased NIA (4/16) were less frequent compared with spots of increased FAF (15/16). Confluent patches of reduced NIA were frequent (12/16), and severely reduced NIA was observed in 3 cases. Areas with reduced NIA corresponded to either increased or reduced FAF. Preservation of subfoveal FAF or NIA corresponded to visual acuity ≥ 0.4. Abnormalities detected with NIA were more extensive or more severe compared to FAF in 15 of 16 patients. Conclusion Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin and their derivates in the pathophysiologic process of ABCA4-RD. NIA imaging provides a noninvasive in vivo visualization of RPE abnormalities that may precede FAF alterations during the degenerative process. Combined FAF and NIA imaging will provide further insight in the development of ABCA4-RD and could help to monitor future therapeutic interventions.