Full-thickness macular hole associated with congenital simple hamartoma of retinal pigment epithelium (CSHRPE).

PURPOSE: To report a unique case of congenital simple hamartoma of retinal pigment epithelium (CSHRPE) associated with full-thickness macular hole (FTMH). METHODS: A 14-year-old female with a previous diagnosis of simple hamartoma of retinal pigment epithelium in the left eye presented with a 3-week onset of reduced visual acuity in the same eye. Complete ophthalmological examination with spectral domain ocular coherence tomography (SD-OCT) and autofluorescence imaging was carried out. Results were compared with the last 4-year follow-up data. RESULTS: On examination, visual acuity in the left eye was counting fingers compared to 20/100 documented in the last follow-up. Fundoscopy revealed a nodular, heavily pigmented, circumscribed foveal mass, with 0.5 mm basal diameter and 1.1 mm thickness corresponding to the simple RPE hamartoma. Although the latter remained unchanged throughout the follow-up period, a new lesion at the inferior edge of the hamartoma was noted. SD-OCT confirmed the presence of a FTMH with no evidence of associated epiretinal membrane, vitreomacular traction or posterior vitreous detachment. After explaining the risks and benefits of vitrectomy for FTMH, the patient declined surgery. CONCLUSIONS: CSHRPE may have associated features such as feeding vessels, retinal surface wrinkling, pigmented vitreous cells, retinal exudation and vitreoretinal adhesion. The case presented herein broadens the clinical spectrum of CSHRPE and emphasizes that despite the benign nature of the lesion, which remains stable without growth, visual loss may occur, attributable to foveal traction and development of FTMH. We postulate that protrusion of the tumor into the vitreous cavity results in tissue stretching and development of anteroposterior and tangential forces which may lead to development of macular hole.

Isoforms of Melanopsin Mediate Different Behavioral Responses to Light.

Melanopsin (OPN4) is a retinal photopigment that mediates a wide range of non-image-forming (NIF) responses to light including circadian entrainment, sleep induction, the pupillary light response (PLR), and negative masking of locomotor behavior (the acute suppression of activity in response to light). How these diverse NIF responses can all be mediated by a single photopigment has remained a mystery. We reasoned that the alternative splicing of melanopsin could provide the basis for functionally distinct photopigments arising from a single gene. The murine melanopsin gene is indeed alternatively spliced, producing two distinct isoforms, a short (OPN4S) and a long (OPN4L) isoform, which differ only in their C terminus tails. Significantly, both isoforms form fully functional photopigments. Here, we show that different isoforms of OPN4 mediate different behavioral responses to light. By using RNAi-mediated silencing of each isoform in vivo, we demonstrated that the short isoform (OPN4S) mediates light-induced pupillary constriction, the long isoform (OPN4L) regulates negative masking, and both isoforms contribute to phase-shifting circadian rhythms of locomotor behavior and light-mediated sleep induction. These findings demonstrate that splice variants of a single receptor gene can regulate strikingly different behaviors.

Resistance to antivascular endothelial growth factor treatment in age-related macular degeneration.

Age-related macular degeneration (AMD) is the main cause of visual impairment and blindness in people aged over 65 years in developed countries. Vascular endothelial growth factor (VEGF) is a positive regulator of angiogenesis and its proven role in the pathological neovascularization in wet AMD has provided evidence for the use of anti-VEGF agents as potential therapies. In this study, we review the literature for the possible causes of failure after treatment with anti-VEGF agents and attempt to propose an algorithm of suggestive actions to increase the chances of successful management of such difficult cases.

Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP) mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.