Diabetes has no additional impact on retinal ganglion cell loss in a mouse model of spontaneous glaucoma.

PURPOSE: There is no valid medical treatment for diabetic retinopathy mostly because its pathogenesis remains largely unknown. Early stages of diabetic retinopathy, just like glaucoma, are characterized by the loss of retinal ganglion cells. Whether the two diseases may share a similar pathogenic background is unknown. METHODS: To clarify this issue the thickness of retinal nerve fiber layer was studied in vivo by optical coherence tomography in 10 Ins2Akita (diabetic) and 10 C57BL/6J (control) mice. The number of retinal ganglion cells and retina's surface covered by neurofilaments were quantified ex vivo in 12 normoglycemic DBA/2J (glaucoma) and 11 diabetic (alloxan-induced) DBA/2J mice (glaucoma + diabetes). RESULTS: At 16 weeks of age retinal nerve fiber layer was significantly thinner in Ins2Akita mice confirming the neurodegenerative impact of diabetes. Number of retinal ganglion cells and retina's surface covered by neurofilaments were similar in normoglycemic and diabetic DBA/2J mice with the exception of the superior quadrant where the number of retinal ganglion cells was increased in animals with glaucoma + diabetes. CONCLUSIONS: In presence of glaucoma, diabetes is unable to induce further retinal ganglion cells loss. The hypothesis that the mechanism leading to retinal ganglion cells loss may be shared by the two diseases cannot be ruled out. Whether early diabetes-driven retinal neurodegeneration could be prevented by neuroprotective treatment proven to be effective in case of glaucoma, remains to be clarified.

New Findings in Early-Stage Keratoconus: Lamina Cribrosa Curvature, Retinal Nerve Fiber Layer Thickness, and Vascular Perfusion.

PURPOSE: Our aim was to investigate the involvement of posterior pole structures in eyes affected by keratoconus (KC). Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to determine the status of lamina cribrosa (LC), peripapillary retinal nerve fiber layer (RNFL), macular and peripapillary microvasculature. DESIGN: Observational, cross-sectional, case-control analysis. METHODS: Single-center investigation involving patients with KC and healthy control subjects. Enrolled subjects underwent anterior segment OCT combined with Placido-disk topography, macular and optic nerve head swept-source OCT and swept-source OCTA scans, and 3D wide glaucoma module for peripapillary RNFL thickness measurement. The LC curvature index was used to express the degree of LC posterior bowing. We calculated the vessel density and vessel length density at the macular superficial capillary plexus, deep capillary plexus, choriocapillaris, and nerve radial peripapillary capillary plexus. RESULTS: Overall, 32 eyes with KC and an equal number of age- and axial length-matched control eyes were included in the analysis. Almost all (97%) of eyes with KC were classified as early stage. KC displayed a reduction in peripapillary RNFL thickness (104.8 ± 11.9 µm vs 110.7 ± 10.5 µm; P = .039) and nerve radial peripapillary capillary plexus vessel density (46.31% ± 3% vs 43.82% ± 4%; P = .006) when compared with control subjects; these differences were more evident in the temporal sector and were associated with a higher LC curvature index (9.9% ± 2.6% vs 8.48% ± 1.7%; P = .012). Mean macular superficial capillary plexus vessel density was 3 percentage points lower in eyes with KC than in healthy controls (P < .001). CONCLUSION: Early-stage KC may be characterized by a posterior bowing of the LC along with a subtle peripapillary RNFL thinning and vascular impairment. These findings support the hypothesis that KC may be a corneal manifestation of a more generalized "eye collagen disease."

Quantitative Optical Coherence Tomography Angiography Detects Retinal Perfusion Changes in Carotid Artery Stenosis.

BACKGROUND: Carotid artery stenosis (CAS) is a multifaceted disease characterized by possible ocular involvement. Treatment with carotid endarterectomy helps to restore cerebral perfusion, which may prevent ocular and cerebral complications. The main aim was to assess retinal and choroidal vascular perfusion changes before and after endarterectomy in patients affected by CAS. METHODS: The design of the study was prospective and observational, including patients affected by CAS and healthy controls. The follow-up was 3 months. We performed quantitative optical coherence tomography (OCT) angiography (OCTA) analyses of retinal perfusion changes, before and after endarterectomy. The main outcome measures were the quantitative changes of choroidal thickness (CT), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL); vessel density (VD); and vessel tortuosity (VT) OCTA metrics were also measured. RESULTS: Sixty eyes of 30 patients affected by CAS and 30 eyes of 30 controls were included. We separately considered the ipsilateral eyes to CAS, the contralateral eyes to CAS, and the healthy eyes. Visual symptoms were absent in all the patients. RNFL and GCL resulted similar between patients and controls (p > 0.05). CT was significantly thinner in ipsilateral eyes than controls (p < 0.01), and it resulted unchanged after surgery (p > 0.05). VD resulted significantly altered only in some plexa of the ipsilateral eyes (p < 0.01), whereas VT disclosed decreased values of the entire retinal vascular network, both in ipsilateral and contralateral eyes (p < 0.05). Endarterectomy was followed by statistically significant improvement of retinal perfusion (p < 0.05). CONCLUSION: Optical coherence tomography angiography can noninvasively detect postendarterectomy retinal perfusion improvements in CAS patients with baseline diabetes and hypertension as a systemic risk factor.

Multimodal imaging of amelanotic choroidal melanoma.

Amelanotic choroidal melanoma (ACM) is an extremely rare malignant tumor affecting the uvea. Because of the complex structure characterizing this kind of lesions, its morphologic features are partially understood, especially if looking to its vascular network. In this paper, we described in details the multimodal imaging features of ACM. Moreover, we disclosed new insights about different orders of blood vessels characterizing this tumor. Despite the entire vascular network is partially detectable by conventional dye-based angiography, it was reconstructed in its entirety by means of optical coherence tomography angiography. In conclusion, multimodal imaging represents a feasible and useful set of tools, able to describe in deep ACM features and its vascular network organization, and to provide clinically relevant information for ACM management.

Multimodal imaging in pediatric arterial macroaneurysm: A case report.

Our aim is to report a case of asymptomatic retinal arterial macroaneurysm in a 9-year-old female patient. She was referred to our Ophthalmology clinic for a routine ophthalmologic examination and, after the detection of a juxtafoveal saccular vascular enlargement in indirect ophthalmoscopy, underwent a multimodal imaging assessment. Optical coherence tomography-angiography and fluorescein angiography were important to determine the nature of the lesion, identified as a congenital retinal arterial macroaneurysm. Retinal vascular abnormalities represent a rare finding in pediatric patients and must be carefully explored to establish the correct diagnosis. A multimodal imaging approach was very useful to thoroughly reach this target. Vascular abnormalities represent a rare finding in pediatric patients and must be carefully explored to establish the correct diagnosis. A multimodal imaging approach is very useful to study in deep the reported arterial macroaneurysm in a non-invasive way.

Vitreomacular traction quantitative cutoffs for the assessment of resolution after ocriplasmin intravitreal treatment.

This study aimed to assess optical coherence tomography (OCT) parameters associated with vitreomacular traction (VMT) resolution after ocriplasmin intravitreal injection and also associated with the development of vitreomacular complications. Study designed was a retrospective case series. Structural OCT images were acquired at baseline and over the follow-up after treatment. We developed a mathematical model to provide quantitative parameters associated with VMT resolution. Moreover, we adopted the same model to assess the quantitative parameters associated with development of further vitreomacular complications or with the worsening of the coexisting condition. Main outcome measures were BCVA, central macular thickness (CMT), VMT reflectivity, VMT size, VMT resolution, epiretinal membrane (ERM), macular holes. 73 eyes of 73 VMT patients (mean age 73 ± 9 years) were recruited. The mean follow-up duration was 2.6 ± 1.1 years. Mean baseline BCVA was 0.38 ± 0.18 LogMAR, improving to 0.26 ± 0.20 at the end of the follow-up (p < 0.01). Baseline CMT was 431 ± 118 µm, improving to 393 ± 122 µm at the end of the follow-up (p < 0.01). 38/73 eyes (52%) showed only VMT, whereas 35/73 eyes (48%) also showed coexisting alterations at baseline. VMT resolved in 40/73 eyes (55% of cases). Our model disclosed VMT reflectivity as the most involved parameter in VMT resolution. VMT size showed less influence on the success of ocriplasmin treatment. ERM was negatively associated with VMT resolution. Moreover, VMT reflectivity values and ERM represented the most important parameters for the onset of vitreomacular complications.

Extrafoveal Müller cells detection in vivo in the human retina: A pilot study based on optical coherence tomography.

Müller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases.

Vessel Density and Vessel Tortuosity Quantitative Analysis of Arteritic and Non-arteritic Anterior Ischemic Optic Neuropathies: An Optical Coherence Tomography Angiography Study.

The aim of this study was to perform quantitative optical coherence tomography angiography (OCTA) assessment of arteritic and non-arteritic anterior ischemic optic neuropathies (AION; NAION). The study was designed as an observational, cross-sectional case series. All patients underwent complete ophthalmologic evaluation including LogMAR best-corrected visual acuity (BCVA), structural optical coherence tomography (OCT) and OCTA images, and dye-based angiography. Retinal nerve fiber layer (RNFL) thickness was obtained from structural OCT, and vessel density (VD) and vessel tortuosity (VT) were measured for each optic nerve head vascular plexus. After selecting the quadrants showing visual field defects, measured by Humphrey 30.2 perimetry (Zeiss Meditec, Dublin, CA, USA), we assessed the correlation between the localization of visual field defects and the quadrants showing impairments of RNFL, VD, and VT. Thirty naïve AION patients (15 arteritic AION (AAION) and 15 non-arteritic AION (NAION)) were included. LogMAR BCVA was 0.6 ± 0.2 for AAION and 0.3 ± 0.3 for NAION (p < 0.01). AAION and NAION eyes showed significant differences in terms of visual field involvement as well as VD and VT values, with remarkably worse alterations affecting AAION eyes. VD values perfectly matched with the quadrants showing RNFL and visual field defects. On the contrary, VT resulted remarkably decreased in all the quadrants, with even worse values in the quadrants showing RNFL and visual field alterations. The present study showed that AAION eyes are more injured than NAION ones. VD represents a good parameter for the detection of the main site on vascular impairment. Remarkably, VT resulted in a more sensitive parameter for the quantitative detection of blood flow impairment in AION disease.

HYPERREFLECTIVE FOVEAL SPOTS IN PATIENTS WITH VITREORETINAL ANOMALIES: A Qualitative and Quantitative Analysis.

PURPOSE: To describe structural optical coherence tomography (OCT) and OCT angiography features in patients who have developed hyperreflective foveal spots with or without vitreomacular interface abnormalities or with vitreous adhesion alone. METHODS: The study design was observational and cross sectional. The presence of defined epiretinal membrane was considered an exclusion criterion. All patients underwent complete ophthalmologic examination, with structural OCT and OCT angiography acquisitions. Both qualitative and quantitative analyses of OCT angiography reconstructions were performed for superficial capillary plexus, deep capillary plexus, and choriocapillaris. RESULTS: Thirty patients (20 men; mean age, 55.2 years) showing hyperreflective foveal spots on structural OCT and 30 healthy control subjects (20 men; mean age, 54.7 years) were enrolled. Best-corrected visual acuity was 0.0 ± 0.0 logarithm of the minimum angle of resolution (20/20 Snellen) for both patients and control subjects. Following global and parafoveal/extrafoveal analyses, both superficial capillary plexus and deep capillary plexus showed significant reduction (P < 0.001). Significant superficial capillary plexus and deep capillary plexus changes were also detected in contralateral eyes (P < 0.001). CONCLUSION: Hyperreflective foveal spots might be seen as the initial effect of traction forces causing Müller cell and external retinal layer disruption, leading to the onset of vitreomacular disease. These changes also have an effect on the retinal vascular network. Further larger prospective studies are necessary to confirm our findings.

Bilateral Choroidal Osteoma Complicated by Bilateral Choroidal Neovascularization.

Choroidal osteoma is a rare, classically unilateral tumor. Less than half of the cases are complicated by the onset of choroidal neovascularization (CNV). The authors describe a case of bilateral choroidal osteoma in a 10-year-old female patient complicated by the onset of bilateral CNV. The diagnosis was made by multimodal imaging and ultrasonography. Best-corrected visual acuity (BCVA) was 20/63 for the right eye (OD) and 20/25 for the left eye (OS). Interestingly, CNV OD resulted exudative, whereas no signs of fluid were detected OS. OCT angiography (OCTA) clearly detected the presence of CNV in both eyes. The patient underwent a single 1.0 mg/0.025 mL aflibercept injection OD. At follow-up, BCVA improved to 20/32 OD after 1 month and to 20/25 after 3 months, with no exudation recurrence. Both BCVA and imaging findings were unremarkable OS, thus suggesting the possible "quiescent" nature of this CNV. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:398-400.].

Reduced vascular perfusion density in idiopathic epiretinal membrane compared to macular pseudohole.

PURPOSE: To investigate the retinal capillary perfusion density by means of optical coherence tomography angiography (OCT-A) in idiopathic epiretinal membrane (ERM) and macular pseudoholes (MPH). METHODS: This observational cross-sectional study examined consecutive patients affected by ERM and MPH presenting between June 2017 and December 2017, as well as the 30 eyes of 30 healthy subjects. All patients underwent swept-source OCT-A examination. For each patient, vessel perfusion density and foveal avascular zone (FAZ) area were measured. RESULTS: Twenty-five eyes of 20 patients with ERM and 28 eyes of 24 patients with MPH were enrolled. Thirty eyes of 30 age-matched healthy controls were included. The perfusion density in the superficial capillary plexus (SCP) of ERM (0.401 ± 0.012) turned out to be inferior that MPH (0.419 ± 0.018) and controls (0.415 ± 0.017) (p < 0.01), while no significant differences were evident among the three subgroups in the deep capillary plexus (DCP) (p = 0.1). The FAZ area in the SCP was smaller in the ERM group (0.168 ± 0.123 mm2), respectively, than MPH (0.295 ± 0.013 mm2) and controls (0.213 ± 0.107 mm2) (p < 0.01), otherwise no difference were noted in the DCP (p = 0.14). CONCLUSIONS: OCT-A morphological features differ between idiopathic ERM and MPH, showing lower perfusion density in idiopathic ERM compared to MPH.

Higher Vascular Density of the Superficial Retinal Capillary Plexus in Degenerative Lamellar Macular Holes.

BACKGROUND AND OBJECTIVE: Optical coherence tomography angiography (OCTA) comparison between vessel density in patients with degenerative-subtype lamellar macular hole (LMH) and healthy individuals. Unaffected fellow eyes were also included in the study. PATIENTS AND METHODS: This observational, cross-sectional study examined 32 eyes affected by unilateral degenerative-subtype LMH, as well as the 32 fellow eyes of the enrolled population. Thirty healthy eyes were used as controls. ImageJ software was used to calculate macular vessel density in the three vascular plexuses (superficial capillary plexus [SCP], deep capillary plexus [DCP], choriocapillaris [CC]) in two regions: (1) a fovea-centered 1.5-mm diameter circular area after subtracting the foveal avascular zone (FAZ) area, obtaining a "ring" in the immediate FAZ proximity (peri-FAZ); (2) the area external to (1) included in the scan. RESULTS: In the peri-FAZ, the SCP of both LMH and fellow eyes showed higher vascular density than in controls (P = .004 for LMH; P = .015 for fellow eye), whereas no difference was evident between LMH and fellow eyes (P = .190). No changes were found in the DCP or the CC. No differences in vessel density of the three plexuses in the area outside the peri-FAZ were evident in any of the three groups. The FAZ in the SCP was larger in the LMH (0.39 ± 0.16 mm2) and in the fellow eye (0.39 ± 0.21 mm2) groups compared with controls (0.27 ± 0.07 mm2; P = .021 for LMH; P = .0043 for fellow eye), whereas it was similar between LMH and fellow eyes (P = .967). CONCLUSIONS: Degenerative-subtype LMH in the immediate proximity of the FAZ has a larger FAZ and higher vascular density in the SCP compared with healthy eyes. Unaffected fellow eyes also have increased vascular density compared with controls. Microvascular changes are evident in both LMH and unaffected fellow eyes and might play a role in disease pathogenesis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e112-e117.].

The Use of OCT and OCT Angiography in Detecting an Atypical Case of Retinal Capillary Hemangioma.

Retinal capillary hemangioma (RCH) is a benign retinal tumor defined by a vascular proliferation localized in the peripheral retina, juxtapapillary retina, or the intraneural portion of the optic nerve. In most cases, diagnosis of RCH is performed by fundus evaluation and confirmed by fluorescein fundus angiography. Nevertheless, a small RCH localized on or adjacent to the optic nerve head could be difficult to detect by fundus examination. Here, the authors report an atypical case of RCH, not ophthalmoscopically visible, but successfully detected first by optical coherence tomography (OCT) and then by OCT angiography, which confirmed its vascular nature. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e81-e83.].

Spectrum of choroidal neovascularisation associated with dome-shaped macula.

AIMS: To investigate the clinical spectrum of choroidal neovascularisation (CNV) in patients with dome-shaped macula with the aid of multimodal imaging. METHODS: In this cross-sectional, retrospective, observational study, we reviewed charts and imaging studies of 144 eyes of 79 consecutive patients with dome-shaped macula evaluated at a tertiary referral centre, including optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICGA). Three masked graders evaluated the prevalence and type of CNV. Primary outcome measures were the diagnostic agreement between OCTA and FA±ICGA, the multimodal imaging characteristics and prevalence of CNV associated with dome-shaped macula. RESULTS: We identified 30 eyes with dome-shaped macula complicated by CNV with an estimated prevalence of 20.8% (95% CI 14.2 to 27.4). Twenty-two eyes (73%) showed a type 2 CNV while eight eyes (27%) showed a type 1 CNV. Serous macular detachment was present in 39 eyes (27%) and harboured a CNV in five cases (13%). The overall diagnostic agreement between OCTA and FA±ICGA was excellent (k=0.894, p<0.001), but only the use of both techniques allowed the identification of the whole pool of CNVs. CONCLUSION: Eyes with dome-shaped macula may either develop typical myopic CNV (ie, type 2 CNV) or pachychoroid-associated CNV (ie, type 1 CNV), similar to those observed in central serous chorioretinopathy. Accordingly, in case of serous macular detachment complicating dome-shaped macula, the presence of an associated CNV should be considered. When suspecting a CNV associated with dome-shaped macula, the application of both OCTA and FA±ICGA is superior to the use of one technique alone.

En Face Optical Coherence Tomography Angiography of Primary Vitreoretinal Lymphoma.

The authors report a case of a female patient affected by primary vitreoretinal lymphoma (PVRL) showing retinal involvement. In particular, multiple subretinal hyperreflective infiltrates were found on optical coherence tomography (OCT). These alterations appeared hyperautofluorescent on fundus autofluorescence images. Interestingly, they also appeared hyperreflective on OCT angiography images. This case report underlined the high utility of OCT-based methodologies in accurately detecting and describing PVRL features. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e173-e174.].

Choroidal Neovascularization in Torpedo Maculopathy Assessed on Optical Coherence Tomography Angiography.

Torpedo maculopathy is characterized by a congenital, unilateral, and torpedo-shaped chorioretinal lesion with unclear pathogenesis and evolution. Although the optical coherence tomography angiography (OCTA) characteristics have already been defined in literature, the authors describe for the first time the presence of choroidal neovascularization (CNV) on the temporal edge of this lesion in a 36-year-old woman with a history of altered visual field in her left eye. The authors' investigation supports the hypothesis of an aberrant choroidal circulation underlying the pathogenesis of this condition, and proves the advantage conferred by OCTA in CNV detection over the other angiographic techniques. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e210-e213.].

Advanced Optical Coherence Tomography Angiography Analysis of Age-related Macular Degeneration Complicated by Onset of Unilateral Choroidal Neovascularization.

PURPOSE: To analyze optical coherence tomography angiography (OCTA) quantitative features in patients affected by new-onset choroidal neovascularization (CNV) in 1 eye and early/intermediate age-related macular degeneration (AMD) in the fellow eye. DESIGN: Case-control study. METHODS: Setting: Clinical practice. STUDY POPULATION: Thirty patients and 30 age-matched controls. OBSERVATION PROCEDURES: Both cohorts underwent complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement, biomicroscopy, fluorescein angiography (FA) and indocyanine green angiography (ICGA) examination, optical coherence tomography, and OCTA scans. The 1-way a test with Bonferroni correction was used to assess statistical significance and Tau Kendall's correlation analysis was performed. MAIN OUTCOME MEASURES: BCVA, choroidal thickness, vessel density, vessel tortuosity, vessel dispersion. and vessel rarefaction. RESULTS: Mean BCVA was 20/32 for CNV eyes and 20/20 for both fellow and control eyes. Choroidal thickness was 190.33 ± 63.98 µm for CNV eyes, 216.83 ± 50.31 µm for fellow eyes, and 310.52 ± 27.13 µm for controls. The quantitative analysis of retinal vessels revealed significant alterations, especially in the deep capillary plexus and radial peripapillary capillaries, both in CNV and in fellow eyes, compared with controls. In particular, decreased vessel density and tortuosity and increased dispersion and rarefaction were found. Several significant correlations were also found among the quantitative parameters adopted. CONCLUSIONS: New postprocessing OCTA parameters are able to detect deep retinal vascular alterations quantitatively, in both CNV-affected and fellow eyes of patients with new-onset CNV. Further investigations are warranted in order to explore the validity of these new approaches on follow-up.

Resolution of cystoid macular edema following arginine-restricted diet and vitamin B6 supplementation in a case of gyrate atrophy.

We report the outcome of 3 years of arginine-restricted diet and vitamin B6 supplementation in a boy who presented with gyrate atrophy of the choroid and retina and bilateral cystoid macular edema. The diagnosis of gyrate atrophy was made on the basis of clinical findings and increased plasma ornithine levels. Molecular genetic testing revealed a disease-causing homozygous mutation in the ornithine aminotransferase (OAT) gene. After 3 months of dietary modification and pyridoxine supplementation, visual acuity improved, and optical coherence tomography showed resolution of cystoid macular edema in both eyes. This anatomical and functional improvement was maintained during 3 years of follow-up.