Torpedo Maculopathy. A Case Report.

AIM: Torpedo maculopathy is an incidental, congenital retinal lesion. The typical clinical finding is a unilateral, symmetric, oval, hypopigmented lesion in the inferotemporal macula. In most cases, the lesion is along the horizontal raphe, is torpedo-shaped, and the nasal edge is directed into the foveola. The diagnosis is determined on the basis of its characteristic shape, localization and findings on optical coherence tomography (OCT). The etiology and pathogenesis of torpedo maculopathy is unclear, but it is believed to be a congenital defect of the retinal pigment epithelium (RPE). The aim of this publication is  highlight this diagnosis and to present an incidental finding of torpedo maculopathy in an adult patient. CASE REPORT: A 30-year-old female patient reported for a routine eye examination. Fundus examination of the right eye revealed an oval hypopigmented lesion with a size of 1 disk diameter inferotemporally from the fovea, which was followed by a satellite lesion in the same axis directed into the foveola. Based on OCT, OCT angiography, fundus autofluorescence, and the typical shape and location of the lesion, the patient was diagnosed with torpedo maculopathy in the right eye. CONCLUSION: In general, torpedo maculopathy is an asymptomatic, congenital, benign retinal lesion, which is mostly diagnosed accidentally during a routine fundus examination. TM is non-progressive retinal finding with a minimal risk of deterioration of visual functions, which does not require any treatment. Nevertheless, due to the rare risk of a choroidal neovascular membrane, it is recommended to examine patients once a year. It is necessary to consider this diagnosis when a unilateral hypopigmented lesion is found inferotemporally from the fovea, and to distinguish it from chorioretinal atrophy, scar, vitelliform dystrophy, or other RPE lesions as part of the differential diagnosis.

ATYPICAL CONGENITAL HYPERTROPHY OF THE RETINAL PIGMENT EPITHELIUM COMPLICATED BY PRESUMED RETINAL PIGMENT EPITHELIAL ADENOMA AND EXUDATIVE MACULOPATHY.

PURPOSE: To report a retinal pigment epithelium (RPE) tumor with exudative maculopathy, originating from an atypical RPE lesion presumed to represent congenital hypertrophy of the RPE or RPE hyperplasia. METHODS: Multimodal imaging including fundus autofluorescence, optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography. RESULTS: A 76-year-old West African man noted visual acuity reduction to count fingers in the right eye and 20/400 in the left eye. Features of chronic glaucoma were noted. In addition, there was a fairly well-circumscribed darkly pigmented RPE lesion in the paramacular region in the right eye, measuring 4 mm in diameter and flat and consistent with atypical congenital hypertrophy of the RPE or RPE hyperplasia. On the posterior margin of this mass was an RPE tumor, presumed to represent RPE adenoma, producing exudative maculopathy and cystoid macular edema. Multimodal imaging was used to distinguish the RPE tumor from macular neovascularization. A similar atypical congenital hypertrophy of the RPE without retinopathy measuring 3.5mm in diameter was noted in the temporal macular region in the left eye. After six monthly doses of intravitreal bevacizumab (1.25 mg/0.05 mL) in the right eye, the maculopathy resolved and the RPE mass showed partial involution with visual acuity return to baseline 20/200. CONCLUSION: Congenital hypertrophy of the RPE and RPE hyperplasia can produce RPE adenoma with related exudative maculopathy. In this case, the maculopathy responded to bevacizumab.

Foveal Congenital Simple Hamartoma of Retinal Pigment Epithelium: A Report of Two Cases.

We report two cases with foveal congenital simple hamartoma of the retinal pigment epithelium (CSHRPE), as both patients presented to our retina services complaining of a unilateral decreased vision. Full ophthalmic examination and multimodal imaging were performed including fundus photography, fundus autofluorescence, optical coherence tomography, fluorescein angiography, and electrophysiological testing. Both patients presented with 20/80 vision in the affected eyes. Foveal CSHRPE was found in both eyes, along with parapapillary hyperpigmented rim, multiple pinpoint macular lesions, and few posterior pole hyperpigmented lesions. Multifocal electroretinogram showed diminished central amplitude in both eyes, with three-dimensional topography map showing blunted foveal peaks in one eye and the absence of a central peak in the other patient. Both patients had a stable vision and clinical examination of the CSHRPE during 5 and 6 years follow up, respectively. Foveal CSHRPE is usually symptomatic and results in a decline in visual acuity. Follow-up of these patients showed stable vision and clinical examination.

The nanophthalmos protein TMEM98 inhibits MYRF self-cleavage and is required for eye size specification.

The precise control of eye size is essential for normal vision. TMEM98 is a highly conserved and widely expressed gene which appears to be involved in eye size regulation. Mutations in human TMEM98 are found in patients with nanophthalmos (very small eyes) and variants near the gene are associated in population studies with myopia and increased eye size. As complete loss of function mutations in mouse Tmem98 result in perinatal lethality, we produced mice deficient for Tmem98 in the retinal pigment epithelium (RPE), where Tmem98 is highly expressed. These mice have greatly enlarged eyes that are very fragile with very thin retinas, compressed choroid and thin sclera. To gain insight into the mechanism of action we used a proximity labelling approach to discover interacting proteins and identified MYRF as an interacting partner. Mutations of MYRF are also associated with nanophthalmos. The protein is an endoplasmic reticulum-tethered transcription factor which undergoes autoproteolytic cleavage to liberate the N-terminal part which then translocates to the nucleus where it acts as a transcription factor. We find that TMEM98 inhibits the self-cleavage of MYRF, in a novel regulatory mechanism. In RPE lacking TMEM98, MYRF is ectopically activated and abnormally localised to the nuclei. Our findings highlight the importance of the interplay between TMEM98 and MYRF in determining the size of the eye.

Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects.

Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely unexplored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histological and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.

Ocular coherence tomography angiography features of congenital hypertrophy of retinal pigment epithelium.

Congenital hypertrophy of retinal pigment epithelium (CHRPE) is a benign, pigmented, flat lesion arising from the retinal pigment epithelium (RPE). In this study, we describe optical coherence tomography angiography (OCTA) features of two eyes with solitary CHRPE. We found that the retinal vasculature over CHRPE was normal in both cases. We observed that in solitary CHRPE, segmentation artifacts can interfere in the interpretation of retinal vasculature due to thinning of the outer retina. Visualization of the underlying choroidal vasculature was obscured to some extent by masking effect of the hyperpigmented RPE. The choroidal vasculature was better appreciated on en face OCTA. On OCTA, the retinal and choroidal vasculature associated with CHRPE was found to be normal in our study.

Coexisting White and Dark Without Pressure Abnormalities Surrounding Congenital Hypertrophy of the Retinal Pigment Epithelium.

The authors report a case of coexisting white and dark without pressure abnormalities surrounding a small congenital hypertrophy of the retinal pigment epithelium and showing corresponding hyperreflectivity and hyporeflectivity of the ellipsoid layer on optical coherence tomography. [J Pediatr Ophthalmol Strabismus. 2019;56:e5-e7.].

Impaired monocyte cholesterol clearance initiates age-related retinal degeneration and vision loss.

Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that drive disease progression. However, mechanisms of drusen and SDD biogenesis remain poorly understood. Although human AMD is characterized by abnormalities in cholesterol homeostasis and shares phenotypic features with atherosclerosis, it is unclear whether systemic immunity or local tissue metabolism regulates this homeostasis. Here, we demonstrate that targeted deletion of macrophage cholesterol ABC transporters A1 (ABCA1) and -G1 (ABCG1) leads to age-associated extracellular cholesterol-rich deposits underneath the neurosensory retina similar to SDD seen in early human AMD. These mice also develop impaired dark adaptation, a cardinal feature of RPE cell dysfunction seen in human AMD patients even before central vision is affected. Subretinal deposits in these mice progressively worsen with age, with concomitant accumulation of cholesterol metabolites including several oxysterols and cholesterol esters causing lipotoxicity that manifests as photoreceptor dysfunction and neurodegeneration. These findings suggest that impaired macrophage cholesterol transport initiates several key elements of early human AMD, demonstrating the importance of systemic immunity and aging in promoting disease manifestation. Polymorphisms in genes involved with cholesterol transport and homeostasis are associated with a significantly higher risk of developing AMD, thus making these studies translationally relevant by identifying potential targets for therapy.

[Torpedo macu-lopathy (clinical case)]. / Makulopatiia 'torpedo' (klinicheskii sluchai).

The article presents a clinical case of torpedo maculopathy. This congenital disorder is most likely to be caused by changes in the retinal pigment epithelium (RPE) during retinal fissure closure. Visual function is usually unaffected and the condition is revealed at routine ophthalmic examination in children and teens. Optical coherence tomography showed the absence of RPE, photoreceptor damage, and massive thinning of the outer nuclear layer at the diseased site without a significant change in the total retinal thickness. RPE involvement was also evidenced by changes in fundus autofluorescence.

Torpedo Maculopathy in a 6-Month-Old Infant: Early Clinical and Optical Coherence Tomography Findings.

A 6-month-old male infant presented for routine ophthalmologic examination. Indirect ophthalmoscopy revealed a flat, oval, hypopigmented lesion located in the temporal macula in the right eye with the tip pointing toward the fovea, which was compatible with torpedo maculopathy. Optical coherence tomography (OCT) was performed at the time of diagnosis. OCT scans of the lesion revealed slight retinal pigment epithelium hyperreflectivity. This case serves as the earliest OCT finding of the youngest patient diagnosed as having torpedo maculopathy in the literature. [J Pediatr Ophthalmol Strabismus. 2017;54:e54-e57.].