FUNCTIONAL DEFICITS ASSOCIATED WITH DARK WITHOUT PRESSURE.

Is it melanoma-associated retinopathy or drug toxicity? Bilateral cystoid macular edema posing a diagnostic and therapeutic dilemma

Macular oedema is a common complication and vision-limiting factor in uveitis. The aim of this study was to compare retinal thickness as measured by optical coherence tomography and photoreceptor function as measured by fundus-related microperimetry with respect to their correlation with visual acuity. Prospective observational monocentre study. Thirty-one patients (53 eyes) with endogenous uveitis and fluorescein angiographically confirmed macular oedema were evaluated. Foveal thickness was analysed using spectral-domain (Spectralis(TM) ; Heidelberg Engineering, Heidelberg, Germany) OCT and retinal sensitivity was assessed using fundus-related microperimetry (MP1; Nidek Technologies, Padova, Italy). All findings were correlated with best-corrected visual acuity (BCVA). Foveal thickness was correlated with BCVA [p = 0.005, r = 0.38, 95% confidence interval (CI) 0.12-0.59]. For microperimetry measurements, a negative correlation with logMAR visual acuity was found. Fixation abnormalities were not associated with poor visual acuity, increased foveal thickness or retinal sensitivity. In eyes with cystoid changes in the outer plexiform and inner nuclear layer, foveal thickness was increased (p < 0.0001). Epiretinal membrane formation was present in 70%. In these eyes, foveal thickness was significantly increased (p = 0.003) and visual acuity was worse (p = 0.08). Foveal thickness and fundus-related microperimetry were correlated with visual acuity. Cystoid changes in the outer plexiform and inner nuclear layer and the presence of epiretinal membrane were associated with poor visual acuity. Fixation abnormalities were not associated with poor visual acuity.

Background: We aimed to measure and correlate inner retinal layer (IRL) thickness and macular sensitivity by optical coherence tomography (OCT) and by microperimetry, respectively, in type 1 diabetes mellitus patients (DM1) without diabetic retinopathy (DR). Methods: Fifty-one DM1 patients and 81 age-matched healthy subjects underwent measurement of the axial length (AL), retinal thickness in the macular ETDRS areas by swept source (SS)-OCT and macular sensitivity by microperimeter. Results: The total retinal and IRL thicknesses were thicker in the DM1 group (p < 0.05) in practically all ETDRS areas, and they had a generalized decrease in sensitivity (p < 0.05) in 9 areas between both groups. There was a significant negative correlation between retinal sensitivity and age in all areas and in visual acuity (VA) in 5 out of the 9 areas for DM1 patients. Only a mild negative correlation was observed between retinal sensitivity in the 5° nasal inner (5NI) area and in IRL thickness in the temporal inner (TI) area (−0.309 with p = 0.029) in the DM1 group. Conclusion: Aging and disease evolution in DM1 patients without DR signs generate a decrease in retinal sensitivity. There was a direct relationship between retinal sensitivity and macular thickness in the DM1 group.

To report a case of pigmentary retinopathy in long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency using multimodal imaging techniques. Case report. An 8-year-old boy with a history of failure to thrive and a diagnosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency was referred for examination. Examination revealed a pigmentary retinopathy with macular atrophy; electroretinography results were consistent with a rod-cone dystrophy. Fundus autofluorescence and optical coherence tomography revealed retinal pigment epithelium atrophy. Follow-up examination findings showed increased severity of retinopathy on electroretinography, with optical coherence tomography angiography revealing enhanced visualization of choroidal vessels. This report reveals that long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency can be characterized as a progressive rod-cone dystrophy, with multi-modal imaging techniques used to describe this condition. In particular, optical coherence tomography angiography can be used to further characterize this condition.

Spectral domain optical coherence tomography (SD-OCT) and photoacoustic microscopy (PAM) were integrated to improve the visualization of retinal vein occlusion (RVO) and retinal neovascularization (RNV). RVO and RNV were observed in living, New Zealand rabbits by Rose Bengal laser-induced retinal vein thrombosis. Multimodal imaging techniques including PAM, OCT, fluorescein angiography (FA), and color fundus photographs were utilized to observe and analyze changes in the retinal vasculature. Spectral domain OCT identified RNV cross-sectional structures, and progressive changes in retinal anatomy due to angiogenesis from the photothermal treatment were monitored at 4, 28, 35, 49, and 90 days post-laser. Compared to alternative methods, PAM in vivo high-contrast imaging possesses the capabilities to accurately visualize the treatment margins of occluded vasculature and areas of RNV. Results were obtained using a laser energy of 80 nJ, which is half a dose below the American National Standards Institute safety limit. The PAM system also demonstrated an increased depth of penetration, which provided high resolution images of the choroid and retinal vasculature when the optical absorption of hemoglobin was used to improve the visualize blood flow. Current modalities of imaging possess the ability to visualize RNV and RVO in two-dimensional and three-dimensional angiography. However, the system integrating both PAM and OCT can better visualize the depth and position of microvessels as well as surrounding structures. This specific multimodal ocular imaging technique may therefore be an improved technology to document minute changes in rabbit eye retinal vasculature while proving to be both safe and efficient.

Mystery of changing choroidal thickness.

We aimed to characterize the vascular phenotypes of an experimental autoimmune retinal uveitis (EAU) model induced by interphotoreceptor retinoid-binding protein (IRBP) using multimodal imaging techniques. We systemically administered IRBP or vehicle to adult C57BL/6 mice. Fundus photography, optical coherence tomography (OCT), in vivo live confocal imaging using different tracers, OCT angiography (OCTA), and electroretinography (ERG) were performed after IRBP immunization. Hematoxylin and eosin and immunofluorescence staining were performed to characterize the immune response and vascular permeability. Mice with EAU exhibited perivascular inflammation, vitritis, and superficial retinal inflammation on fundus photography and OCT. H&E revealed immune cell infiltration in the perivascular area of the retina and choroid accompanied by a significant degree of perivasculitis that subsequently damaged photoreceptors 3 weeks postimmunization. Immunofluorescence staining showed subsequent transcytosis induction after local microglial activation followed by neutrophil recruitment in the perivascular area. Transcytosis in the superficial and deep vascular areas was improved by immune cell suppression. Intravital in vivo confocal imaging showed signs of neutrophil infiltration and obstructive vasculitis with perivascular leakage 3 weeks postimmunization. OCTA revealed a significant decrease in vascular flow in the deep capillary layer of the retina. Functional analysis showed that scotopic responses were intact at 2 weeks; however, normal photopic and scotopic responses were hardly detected in mice with EAU mice at 3 weeks postimmunization. Our data suggest that inflammatory cell activation and subsequent transcytosis induction in endothelial cells might be a major pathogenic factor for vascular leakage in uveitis, providing new insights into the pathophysiology of retinal vasculitis in noninfectious uveitis.

To evaluate cone morphology, retinal sublayer thicknesses and vessel density (VD) and their associations with retinal sensitivity (RS) in red-green colour vision deficiency (CVD). 36 patients with red-green CVD and 38 age-matched controls were enrolled. Diagnosis was confirmed by pseudoisochromatic plates and the Farnsworth-Munsell 100-hue test. All participants underwent adaptive optics scanning laser ophthalmoscopy (AO-SLO), optical coherence tomography (OCT), OCT-angiography and microperimetry. Patients with red-green CVD exhibited significantly decreased cone density and regularity, increased cone dispersion and spacing at 3° eccentricity, and thinner myoid and ellipsoid zone (MEZ) and outer segment (OS) (all p<0.01). VDs, blue-yellow error score and axial length did not differ between groups. Patients with CVD had higher red-green error scores and lower RS (p<0.05). Temporal cone density was correlated with RS only in CVD (r=0.410, p=0.011). Mean cone density correlated with favourable cone parameters and MEZ thickness (r=-0.827 to 0.862, p<0.005) and predicted higher RS (r=0.463, p<0.001). Red-green CVD features reduced cone density, disorganised arrangement and MEZ and OS thinning, which are closely linked to RS. Cone structural integrity has clinical value for managing visual impairments in CVD.

PurposeTo describe the features of a choroidal macrovessel (CM) in multimodal imaging and underline the importance of non‐invasive imaging techniques.MethodsA 78‐year‐old man presented to our department for alteration of central vision of the right eye after uneventful cataract surgery. The patient had a complete ophthalmic examination with best corrected visual acuity (BCVA) measurement and slit lamp examination. Multimodal imaging was performed including fundus autofluorescence (FAF), Swept‐Source Optical Coherence Tomography (SS‐OCT), en‐face OCT, OCT‐angiography, Fluorescein Angiography (FA) and Indocyanine Angiography (ICG‐A).ResultsBCVA was 20/50 in the right eye and 20/80 in the left eye. Anterior segment examination was unremarkable except for a nuclear cataract in the left eye. Funduscopic examination showed a subretinal tortuous lesion starting in the fovea and extending toward the temporal periphery in the right eye and was normal in the left eye. FAF of the right eye showed increased autofluorescence of the lesion retracing its serpiginous shape. SS‐OCT revealed a choroidal hollowness. This lesion had a pattern corresponding to a choroidal macrovessel on en‐face OCT scans with a similar signal to the physiological choroidal vessels. OCT‐A showed a low signal within the choroidal vessel. FA of the right eye showed an early serpentine‐shaped hyperfluorescence and ICG‐A revealed early prominent filling with late hypofluorescence and persisting laminar flow. A choroidal macrovessel (CM) was diagnosed.ConclusionsCM is a rare entity that is not always easy to recognize. ICGA is the most valuable tool for its diagnosis when the presentation is not typical. In cases of CM with a well delineated pattern, non‐invasive imaging modalities and particularly SS‐OCT and en‐face OCT can be very helpful for the diagnosis while avoiding dye injection.

To assess if drusen volume can serve as structural clinical outcome marker in Malattia Leventinese, and to evaluate whether cones or rods are more affected by its progression, using multimodal imaging and mesopic and two-color scotopic microperimetry. This was a prospective monocentric cross-sectional cohort study of participants with genetically confirmed Malattia Leventinese. Participants were classified according to morphology. Mean drusen volume, calculated from spectral-domain optical coherence tomography, was compared with microperimetry parameters (mesopic retinal sensitivity, scotopic red and cyan function, difference between scotopic cyan-red function). Fourteen participants (28 eyes) were enrolled. Mean drusen volume increased (bilaterally P = 0.028) and mesopic retinal sensitivity decreased with later stage (right eye: P = 0.028; left eye: P = 0.050). Scotopic microperimetry showed that scotopic cyan function was lower than scotopic red function in moderate stage. Scotopic red function decreased in severe stage. Mean drusen volume correlated to mesopic retinal sensitivity (right eye: P < 0.001; left eye: P = 0.007). Retinal sensitivity diminishes with Malattia Leventinese progression. Rod function declines before cone function, whereas at late stages, cone loss predominates. Drusen accumulation, initially speckled around the macula and optic disc and confluent with disease progression, correlates well with visual function loss and impaired quality of life. Thus, therapeutically reducing drusen accumulation could be efficacious.

In this study, our goal was to deepen the understanding of the clinical significance and underlying pathogenic mechanisms of the hyperreflective ganglion cell layer (HGB) observed in optical coherence tomography (OCT) scans of patients with retinitis pigmentosa (RP). The study was designed as observational, cross-sectional. RP patients with and without HGB were recruited and underwent complete multimodal retinal imaging assessment, including OCT, OCT angiography (OCTA) and Dense Automatic-RealTime (DART) OCTA. Morphological outcome measures included OCTA vessel density (VD), foveal avascular zone area and ellipsoid zone (EZ) width. Functional outcome measures were LogMAR best-corrected visual acuity (BCVA) and retinal sensitivity. Twenty eyes with HGB (20 RP patients) and 20 eyes without HGB (20 RP patients) were included. A reference control group was included as well. RP eyes with HGB were characterized by significantly worse LogMAR BCVA and retinal sensitivity, compared with RP eyes without HGB. Moreover, HGB subgroup showed significantly worse VD values of intraretinal capillary networks. The main superficial capillary plexus (SCP) VD reduction was detected in the extrafoveal region. DART OCTA allowed to support the SCP perivascular gliosis pathogenic origin of HGB. DART OCTA was able to detect (I) SCP perivascular hyperreflectivity; (II) SCP perfusion signal reduction and (III) peripheral SCP capillaries closure. The presence of HGB is identified as an adverse finding in a subset of eyes affected by RP. HGB correlates with markedly deteriorated retinal morphology and function. The possible pathogenic mechanism underlying HGB manifestation is the perivascular gliosis of the SCP.

Choroidal osteoma is a rare benign ocular tumor, with neovascular complications being even less common. The diagnosis is greatly facilitated by multimodal imaging techniques. However, treatment remains a challenge, as no standardized protocols exist, and current approaches rely primarily on intravitreal injections of anti-VEGF agents. We describe the case of a 45-year-old patient with no significant medical history who presented in 2020 with a progressive macular syndrome, characterized by decreased visual acuity and a central scotoma over several months. Ophthalmologic examination of the right eye was unremarkable, while the left eye showed reduced visual acuity of 3/10. The anterior segment was normal with a clear lens. Fundoscopy revealed a well-demarcated yellowish juxta-papillary subretinal lesion extending into the papillomacular area. Optical coherence tomography (OCT) demonstrated serous retinal detachment, intraretinal macular edema, and retinal pigment epithelial (RPE) detachments, along with a juxta-papillary eovascular membrane. A-scan ultrasonography confirmed the diagnosis of choroidal osteoma, showing a hyper-echogenic lesion with posterior shadowing. Retinal angiography and indocyanine green angiography (ICG) revealed occult neovascularization extending into the papillomacular area. The patient was treated with intravitreal anti-VEGF injections. Although the therapeutic response was gradual, injections every six weeks successfully maintained visual acuity at 7/10 and resolved the intra- and subretinal fluid. The management of neovascular complications in choroidal osteoma remains complex due to the absence of standardized treatment protocols. Anti-VEGF therapy shows promise, albeit with a slow response, and requires sustained long-term administration to optimize visual outcomes and preserve visual function.

Foveal hypoplasia is a retinal disorder in which the foveal pit of the macula lutea is incompletely developed and is characterized by nystagmus and low visual acuity. It can manifest itself in isolation, without a clear etiology, or associated with other conditions such as albinism, aniridia, Stickler Syndrome, optic nerve hypoplasia, microphtalmus, etc. Modern retinal imaging technologies are key to diagnosis of this rare retinal disorder. We present a case of a 19-year-old woman with poor distance and near vision and nystagmus since childhood, without other associated diseases. Visual acuity was 0.5 Snellen decimal units in both eyes, with present latent nystagmus. The anterior segment was normal, while an absent foveal reflex was found on fundus examination. Optical coherence tomography (OCT) imaging confirmed the absence of foveal depression in the macular area. OCT-angiography (OCTA) was performed, which confirmed the absence of a foveal avascular zone in the macula. According to the proposed grading system parameters for foveal hypoplasia, this case corresponds with the most severe (grade 4) degree of foveal hypoplasia. Foveal hypoplasia can be associated with numerous etiological factors, and visual acuity can vary depending on the development of foveal photoreceptors and structural gradation. For this reason, especially in children with reduced visual acuity of unknown etiology and the existence of nystagmus, it is recommended to perform additional examinations and use multimodal imaging techniques (OCT and OCTA) in order to make a timely and accurate diagnosis. Management of this disorder includes treatment of the associated ocular and systemic conditions, refractive correction, treatment of amblyopia and use of low vision aids.&#x0D;

Introduction Variants in the RCBTB1 gene have recently been described in patients with inherited retinal disease; so far, there is limited knowledge about this entity, differential diagnoses, and disease progression. Here, we report a novel splice variant in RCBTB1 and describe the associated retinopathy. Methods Clinical assessment included multimodal imaging with optical coherence tomography, blue-light fundus autofluorescence, and near-infrared fundus autofluorescence. Atrophy progression was evaluated over time. Genetic testing was conducted by next-generation sequencing, pathogenicity was assessed by in silico analysis. Results A 54-year-old woman presented with a best-corrected visual acuity of 20/50 in the right and 20/63 in the left eye, respectively. Fundus examination showed macular and peripapillary atrophy with foveal sparing, as well as granular alterations extending to the mid-peripheral retina. Genetic testing revealed a novel splice variant (c.1325-2A>G) in intron 11 of RCBTB1. Discussion We confirm that RCBTB1-associated retinal dystrophy shares phenotypic similarities with mitochondrial retinopathy. Multimodal retinal imaging is vital to assess disease progression and may facilitate a better understanding of this pathology.

Choroidal osteoma (CO), also known as osseous choristoma, is a rare benign osseous tumour of the choroid. It is diagnosed based on the presence of a yellowish-white to orange lesion deep in the retinal pigment epithelium (RPE) with well-defined margins and bone density in ultrasonography (Pellegrini et al. 2014). Patients are usually asymptomatic and the lesion is found incidentally. Choroidal neovascularization (CNV) is the most frequent complication of CO and leads to severe visual impairment. Anti-vascular endothelial growth factor (Anti-VEGF) therapy has been recommended for CNV-related CO (Song & Roh 2009). Here, we report a case of extrafoveal CO associated with CNV. A 75-year-old woman, incidentally diagnosed with CO at the age of 68 years, presented with a two-month history of metamorphopsia in the left eye. Best-corrected visual acuity (BCVA) was 0 logMar in the right eye and 0.7 logMar in the left eye. Anterior segment findings were unremarkable in both eyes. A fundus examination of the right eye was unremarkable, whereas, in the left eye, it revealed a yellowish-white area with small haemorrhages in the superior temporal retina that suggested an extrafoveal CO associated with CNV (Fig. 1A,B). Baseline evaluation of the right eye. (A, B) Colour fundus photography and multicolour image showing the choroidal osteoma with subretinal haemorrhage. The black circle underlines macular haemorrhage spots. (C−E) Optical coherence tomography (OCT) angiography, fluorescein angiography and indocyanine green angiography revealed late-stage choroidal neovascularization within the tumour. The red circle underlines macular haemorrhage spots (F, G) A and B scan echography showed a slightly elevated choroidal mass with high reflectivity and acoustic shadowing. (H) Enhanced depth imaging optical coherence tomography (EDI-OCT) showed a hyper-reflective mass in the subretinal space associated with a neurosensory detachment and detected a sponge-like structure of the choroid. (I, J) Fluorescein and indocyanine angiography of the superotemporal region of the contralateral normal eye. (K) Optical coherence tomography (OCT) scan of the macular region without any pathological feature. (L−P) Colour fundus photography, multicolour image, fluorescein angiography and indocyanine green angiography and OCT angiography showing regression of the choroidal neovascularization after four months of treatment. (Q) Enhanced depth imaging optical coherence tomography (EDI-OCT) revealed resolution of the subretinal fluid. [Correction added on 17 June 2016 after first online publication: Figure 1 has been replaced to correct the labelling of Fig. 1E and 1O]. Optical coherence tomography (OCT) angiography (angiovue software RTVue; Optovue Inc., Fremont, CA, USA) showed a hyporeflective area surrounded by a hyper-reflective-edged ring in direct relation to the osteoma. It also showed a dense irregular vascular network within the tumour in the outer retinal layer and choroid capillary layers. Moreover, the CNV detected in the choroidal layer had fine glomerular-like hyper-reflection (Fig. 1C). Visualization of vessels is better with non-invasive OCT angiography than with fluorescein angiography (FA) and Indocyanine green angiography (ICGA); in fact, with the latter two techniques, the leaking vessels of the CNV usually are overshadowed by the dye in the late phases (Wang et al. 2015). Fluorescein angiography (FA) showed early hyperfluorescence due to leakage surrounded by an area of blocked fluorescence, and late staining of the lesion showed well-defined borders (Fig. 1D). Indocyanine green angiography (ICGA) confirmed the presence of an active CNV secondary to CO (Fig. 1E). Standardized A and B scan echography revealed a slightly elevated choroidal mass with high reflectivity and acoustic shadowing (Fig. 1F,G). Enhanced depth imaging optical coherence tomography (EDI-OCT) performed with the Heidelberg Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) showed a hyper-reflective mass in the subretinal space associated with neurosensory detachment and elongation of the outer segments. Enhanced depth imaging optical coherence tomography (EDI-OCT) also revealed a sponge-like structure of the choroid with horizontal tubules (Fig. 1H). The findings obtained in our patient strongly support the diagnosis of OC as opposed to sclerochroidal calcification (SCC). In fact, unlike OC, SCC does not feature growth, decalcification or intralesional vessels of CNV, as recently reported by Shields et al. (2015). After obtaining informed consent, we administered three monthly intravitreal injections of ranibizumab in the left eye. Four months later, the patient's BCVA was 0.1 logMar, and a fundus examination revealed resolution of the subretinal haemorrhage (Fig. 1L,M). Fluorescein angiography (FA) and ICGA showed regression of the CNV (Fig. 1N,O) and spectral domain OCT revealed no subretinal fluid (Fig. 1Q). Optical coherence tomography (OCT) angiography demonstrated a smaller and more rarified vascular network inside a capsular formation (Fig. 1P). These findings remained unchanged during the 12-month follow-up. In summary, OCT angiography reveals unique features in the vascular changes of CNV in CO not visualized with other imaging methods. However, additional studies are needed to verify whether this technique can partially replace FA and ICGA in the diagnosis and follow-up of CNV secondary to CO.