[Morphology of outer retinal tubulations in the outcome of exudative age-related macular degeneration according to optical coherence tomography angiography]. / Morfologiya naruzhnykh retinal'nykh tubulyatsii v iskhode vlazhnoi formy vozrastnoi makulyarnoi degeneratsii po dannym opticheskoi kogerentnoi tomografii s funktsiei angiografii.

Outer retinal tubulation (ORT) develops in the later stages of age-related macular degeneration (AMD). It is associated with low visual acuity, severe loss of photoreceptors, choroidal neovascularization (CNV), and geographic atrophy. Despite the frequent detection of ORTs by optical coherence tomography (OCT), their role in the process of outer retinal atrophy and degenerative changes in photoreceptors remains undetermined. PURPOSE: To investigate the evolution of ORT in patients with exudative and disciform-stage CNV. MATERIAL AND METHODS: The retrospective study included 340 patients with AMD, among them 235 (69%) women and 105 (31%) men with mean age of 76±7.4 years; in all, the analysis involved 267 eyes with dry AMD and 174 eyes with CNV: 92 eyes - with exudative AMD, 82 eyes - with disciform-stage disease). In addition to standard OCT, all patients underwent OCT-angiography (OCTA). In 10 cases, patients with exudative AMD were followed up after intravitreal injections of Aflibercept. RESULTS: ORTs were detected in 37 eyes of 32 patients (26%), all of them with CNV: 13 eyes with exudative AMD (group 1) and 24 eyes with disciform scar (group 2; p=0.013).The groups were similar in the type and morphology of ORTs. The most common were closed, i.e. fully formed ORT (92% of cases in group 1, and 88% in group 2). Destruction of the ellipsoid zone associated with ORT was observed in both groups. In one case, there was an increase in the size of ORT corresponding to the volume of cystic macular edema. Disappearance of ORT was noted only in one of ten patients 3 months after intravitreal injection of Aflibercept, but was not accompanied by visual acuity improvement. CONCLUSION: Outer retinal tubulations are more common in the later stages of AMD, being an indicator of a deep destructive process in photoreceptors. In exudative AMD, ORTs serve as a predictive marker for poor functional outcomes.

Peripapillary comet lesions and comet rain in PXE-related retinopathy.

PURPOSE: To study peripapillary comet lesions (PCL) in Italian patients affected with pseudoxanthoma elasticum (PXE). METHODS: Retrospective review of fundoscopic and swept-source (SS) optical coherence tomography (OCT) images of patients with PXE examined at the Regional Reference Center for Hereditary Retinal Degenerations at the Careggi Teaching Hospital of Florence from 2012 to 2017. RESULTS: From 148 eyes of 74 patients affected with PXE, we identified 24 eyes of 14 patients (11 were female) with a mean age of 39 years (range, 20-58 years) characterized by peripapillary comet lesions. Of these 24 eyes, 15 eyes (of 10 patients) were characterized by comet rain. The smallest comet lesion at the OCT examination appeared as a focal roundish hyper-reflective alteration at the level of the outer retinal segments and RPE-Bruch's membrane complex; the larger lesions appeared as circular and ovoid structures with hyper-reflective borders in the outer nuclear layer. CONCLUSION: The comet lesion formation process involves the outer layers of the retina and RPE/Bruch's membrane complex. It consists of a degenerative/rearrangement process of the photoreceptors which occurs in an area of focal altered RPE/Bruch's membrane resembling the outer retinal tubulation.

The effect of ranibizumab and aflibercept treatment on the prevalence of outer retinal tubulation and its influence on retreatment in neovascular age-related macular degeneration.

BACKGROUND: We aimed to analyze the differences in the prevalence of outer retinal tubulation (ORT) in neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents, either aflibercept or ranibizumab. Our further aim was to examine the changes in the frequency of injections of ranibizumab before and after ORT appearance. METHODS: Two hundred thirty six eyes of 230 patients were included in the study (184 eyes treated with ranibizumab by pro re nata regimen (PRN), 52 eyes with aflibercept bimonthly) and followed for 6-24 months. Using optical coherence tomography (OCT), the first appearance of ORT was documented, and fixed time point evaluations were also made every six months to determine the existence of ORT. The number of injections, the presence or absence of subretinal hyperreflective material (SHRM) at treatment initiation and visual acuity were also noted. RESULTS: The survival analysis with Cox proportional hazard model showed no significant difference between the ranibizumab and aflibercept groups in relation to the development of ORT (p = 0.79, hazard ratio 0.92). In the PRN treated ranibizumab group the number of injections showed significant decrease after ORT development (p = 0.004). When SHRM was present at treatment initiation the chance of developing ORT was 2.75 and 11.14 times higher in the ranibizumab and aflibercept groups, respectively. CONCLUSIONS: The prevalence of ORT increased over time independently from the chosen anti-VEGF drug. Our results suggest that upon the appearance of ORT a decrease in retreatments can be expected.

[Characteristics and Clinical Significance of Outer Retinal Tubulation in Wet Age-macular Degeneration Treated by Anti-vascular Endothelial Growth Factor Through Optical Coherence Tomography.]

OBJECTIVES: To determine the characteristics and clinical significance of outer retinal tabulation (ORT) in wet age-related macular degeneration (wAMD) treated by anti-vascular endothelial growth factor (anti-VEGF) through optical coherence tomography (OCT). METHODS: The 35 wAMD patients with 39 ORT eyes treated by anti-VEGF were examined by OCT to determine the morphological features and evolution of the ORTs over time and their response to anti-VEGF. RESULTS: ORTs were located in the places that exudation or edema had happened in the outer nuclear layer of retina.38 ORTs remained stable on both quantity and morphology.One ORT became invisible temporarily and then reappeared. CONCLUSIONS: ORTs are reconstructed by photoreceptor cells that have survived after outer retina damages.There is no connection between anti-VEGF treatment and ORT formation.

Outer retinal tubulations in central serous chorioretinopathy associated with choroidal neovascularisation.

AIM: To report the prevalence and characteristics of outer retinal tubulations in eyes with choroidal neovascularisation associated with chronic central serous chorioretinopathy. METHODS: Retrospective case series which included evaluation of optical coherence tomography B-scans and enface optical coherence tomography scans of eyes with choroidal neovascularisation associated with chronic central serous chorioretinopathy. The characteristics of outer retinal tubulations such as number, shape and distribution were noted. The location of the outer retinal tubulations was correlated with autofluorescence. RESULTS: Outer retinal tubulations were detected in 9.1% of the eyes (9 out of 87 eyes). The average number of outer retinal tubulations in each eye was 4.7 ± 4.6. Spheroidal outer retinal tubulations were more common than the branching tubules. Although presence of outer retinal tubulations was mostly associated with inactive disease, two eyes had coexistent subretinal fluid. CONCLUSION: Outer retinal tubulations associated with choroidal neovascularisation in chronic central serous chorioretinopathy, though less frequent, when present are more numerous, mostly extrafoveal and more spheroidal in shape compared to outer retinal tubulations associated with age-related macular degeneration and other degenerative conditions.

Outer retinal tubulation and inner retinal pseudocysts in a patient with maternally inherited diabetes and deafness evaluated with optical coherence tomography angiogram.

A 47-year-old lady (index case) with diabetes and deafness showed multiple oval circumferential areas of perifoveal atrophy in both eyes. Autofluorescence revealed areas of hypoautofluorescence. Optical coherence tomography (OCT) showed depression of inner retinal surface, inner retinal hyporeflective spaces (pseudocysts), disorganization/thinning of outer retina, outer retinal tubulation, loss of external limiting membrane, ellipsoid and interdigitation zone, and thinning of the retinal pigment epithelium and choriocapillaris. The patient was evaluated using OCT angiogram. Retinal lesions of her mother (68-year-old) were very obvious on autofluorescence imaging. The result of A3243G mutation in MTTL1 gene was positive in the index case confirming the diagnosis of maternally inherited diabetes and deafness (MIDD).

Outer retinal tubulations in maternally inherited diabetes & deafness - associated macular dystrophy: case report.

PURPOSE: To describe the presence of outer retinal tubulations (ORTs) in a patient diagnosed with maternally inherited diabetes and deafness (MIDD) - associated macular dystrophy. METHODS: The patient underwent clinical examination assessing best-corrected visual acuity (BCVA), anterior segment evaluation and fundoscopy followed by optical coherence tomography (OCT). Audiological evaluation was also performed for the accurate diagnosis of MIDD. RESULTS: A 57-year-old diabetic patient with mildly affected BCVA, macular dystrophy and severe neurosensory hearing loss was diagnosed with MIDD. Examination with OCT revealed the central loss of photoreceptors and the presence of ORTs in close proximity to the fovea. Regular follow-up seven months after her initial visit showed no alterations in the clinical and imaging status of the patient. In the context of family screening, the patient's sister presented with the diagnosis of pre-diabetes and a moderate sensorineural hearing loss, while fundus examination and OCT revealed no significant pathology. In this report, we present ORTs in association with MIDD. CONCLUSIONS: ORTs are a non-specific finding that can be found in MIDD and other retinal dystrophies. Taking under consideration the rarity and the difficulty in diagnosing this entity, our data could serve as an addition to the existing knowledge in terms of clinical and imaging manifestations of MIDD.

Prevalence of outer retinal tubulation in eyes with choroidal neovascularization.

BACKGROUND: Outer retinal tubulations (ORTs) are branching tubular structures located in the outer nuclear layer of the retina. The goal of this study is to determine the prevalence of ORTs observed in eyes with choroidal neovascularization (CNV) undergoing treatment with anti-angiogenic intravitreous injection (IVI) with anti-VEGF (vascular endothelial growth factor) at the Ophthalmology Department of a tertiary hospital in São Paulo, Brazil. METHODS: This is a descriptive study based on medical charts and Spectral-domain Optical Coherence Tomography (Sd-OCT) scans of 142 patients (158 eyes) treated between 2012 and 2014 with IVI of anti-VEGF for CNV. The patients' data was analysed according to age, gender, pathology, presence of ORTs, and best corrected visual acuity (BCVA). Patients with and without ORTs were compared according to the last BCVA obtained using Chi square corrected by the Yates factor. RESULTS: ORTs were found in a total of 40 out of 158 eyes (25.31 %) with CNV; in 33 out of 119 eyes (27.7 %) with neovascular age-related macular disease (AMD); in 5 out of 8 eyes (62.5 %) with neovascular angioid streaks; and in 2 out of 12 eyes (16.67 %) with myopic neovascular membranes. Most patients with ORTs had BCVA worse than 20/200, significantly worse BCVA than patients without ORTs. CONCLUSIONS: Recent studies have considered that the presence of ORTs is indicative of a photoreceptor degeneration process and may represent a final stage of multiple retinal degenerative pathologies. The prevalence of ORTs in eyes with CNV has not been well described, especially when considering the Brazilian population treated in a public health care system. In our study, ORTs were observed in only three different pathologies: neovascular AMD, neovascular angioid streaks and myopic neovascular membranes. The correct recognition of ORTs is fundamental for its differentiation from intraretinal cysts, for the latter is related to the activity of neovascular diseases, and usually guides anti-angiogenic therapy. We conclude that ORTs have a high prevalence in the population studied, and their correct identification presents relevant therapeutic implications.

Outer retinal tubulation in diabetic macular edema following anti-VEGF treatment.

BACKGROUND: To address the presence and features of outer retinal tubulation (ORT) found in diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF) and to differentiate between ORT and cystoid DME, which have different plans of management. METHODS: This was a retrospective review of a total of 514 patients investigated with spectral domain optical coherence tomography (OCT) in patients with diabetic macular edema treated with anti-VEGF. ORT was seen in 12 eyes of 11 patients. The morphologic characteristics of ORT and its progress over time were examined using OCT data. The retinal images were obtained by horizontal and vertical scans to analyze the possible presence of ORT and to explore their morphologic features and location in the retinal layers. RESULTS: ORT was seen in DME treated with anti-VEGF. ORT was shown as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 30 to 120 µm high and 30 to 1775 µm wide. The tubules generally remained stable over time. In a retinal practice specializing in advanced diabetic retinopathy clinic, this ORT was seen in 12 eyes of 11 patients during a 12-month period. ORT presented either after receiving 0.05 mL open-label intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab. CONCLUSION: ORT is found in DME treated with anti-VEGF that may show damage to the outer retina secondary to the severity and chronicity of the DME. ORT may be a result of underlying chronic and severe diabetic macular edema that may occur later possibly secondary to retinal layers rearrangement after several anti-VEGF injections. It is important to differentiate between ORT and cystoids DME. The presence of the ORT entity alone without the presence of DME does not require further anti-VEGF re-injections.