Update on Retinal Vein Occlusion.

Retinal vein occlusion represents the second leading cause of retinal vascular disorders, with a uniform sex distribution worldwide. A thorough evaluation of cardiovascular risk factors is required to correct possible comorbidities. The diagnosis and management of retinal vein occlusion have changed tremendously in the last 30 years, but the assessment of retinal ischemia at baseline and during follow-up examinations remains crucial. New imaging techniques have shed light on the pathophysiology of the disease and laser treatment, once the only therapeutic option, is now only one of the possible approaches with antivascular endothelial growth factors and steroid injections being preferred in most cases. Nowadays long-term outcomes are better than those achievable 20 years ago and yet, many new therapeutic options are under development, including new intravitreal drugs and gene therapy. Despite this, some cases still develop sight-threatening complications deserving a more aggressive (sometimes surgical) approach. The purpose of this comprehensive review is to reappraise some old but still valid concepts and to integrate them with new research and clinical data. The work will provide an overview of the disease's pathophysiology, natural history, and clinical features along with a detailed discussion on the advantages of multimodal imaging and of the different treatment strategies with the aim of providing retina specialists with the most updated knowledge in the field.

Eye-selfie to resolve the enigmatic diagnosis of transient "eye spot".

PURPOSE: To describe two cases of Cobb's tufts in apparently healthy subjects. METHODS: Observational case series. RESULTS: Two patients reporting sudden vision loss, with subsequent complete recovery, underwent a complete ophthalmological examination, including iris fluorescein angiography. Both patients took an "eye-selfie" using their smartphone to provide evidence of the iris bleeding. Iris fluorescein angiography confirmed the presence of iris neovascular tufts at the pupillary margin. CONCLUSION: Diagnosis of Cobb's tufts can frequently be challenging. The two patients' astute action in taking photographs of the eye enabled the condition to be promptly identified.

OCT retinal angiography features in patients with rheumatoid arthritis: A pilot study.

PURPOSE: To evaluate the superficial (SCP) and deep retinal capillary plexus (DCP) by mean of optical coherence tomography angiography (OCTA) in treatment-naïve patients affected by rheumatoid arthritis (RA). METHODS: Between March 2019 and January 2020, patients with recent diagnosis of "definite RA" based on 2010 Rheumatoid Arthritis Classification Criteria were included in a Prospective, observational single center case-control study carried out at G.B. Bietti Foundation. Data were compared with those of 16 healthy age- and sex-matched subjects. Values of the vessel density (VD) of SCP and DCP, central foveal thickness (CFT), foveal avascular zone (FAZ) were collected by mean of OCTA. Main outcome measure was the VD alteration of SCP and DCP in treatment-naïve RA-patients. RESULTS: No difference in age, sex-distribution, best-corrected visual acuity, CFT was registered between the two groups. OCTA data analysis showed in RA-patients a statistically significant reduction in the VD in the mean global area, inner ring, especially in the superior quadrant of the SCP. A trend of VD reduction was also registered in temporal, nasal, and inferior quadrants, respectively, although it did not reach a statistically significant value. Assessment of VD of DCP and FAZ area did not evidence any difference among the groups. CONCLUSIONS: OCTA allows to highlight the vascular remodeling of the retinal microcirculation in RA-patients, even in early stages of the disease, demonstrating a reduction of VD. Outcomes of the current investigation can provide new insight in the pathogenetic mechanism of RA and extend the potential applications of this diagnostic tool.

The Role of Imaging in Planning Treatment for Central Serous Chorioretinopathy.

Central serous chorioretinopathy (CSC) is a controversial disease both in terms of clinical classification and choice of therapeutic strategy. Choroidal layers, retinal pigment epithelium (RPE), photoreceptors, and retina are involved to varying degrees. Beyond well-known symptoms raising the clinical suspect of CSC and slit-lamp fundus examination, multimodal imaging plays a key role in assessing the extent of chorioretinal structural involvement. Subretinal fluid (SRF) originating from the choroid leaks through one or multiple RPE defects and spreads into the subretinal space. Spontaneous fluid reabsorption is quite common, but in some eyes, resolution can be obtained only after treatment. Multiple therapeutic strategies are available, and extensive research identified the most effective procedures. Imaging has carved a significant role in guiding the choice of the most appropriate strategy for each single CSC eye. Multiple biomarkers have been identified, and all of them represent a diagnostic and prognostic reference point. This review aims to provide an updated and comprehensive analysis of the current scientific knowledge about the role of imaging in planning the treatment in eyes affected by CSC.

Large choroidal excavation in pachychoroid disease: A case report.

PURPOSE: To report the morphological and clinical features of a case of pachychoroid disease with focal choroidal excavation and large choroidal excavation complicated by choroidal neovascularization. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity assessment, anterior segment and dilated fundus examination, fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography. RESULTS: During the previous follow-up, the 57-year-old man received a diagnosis of central serous chorioretinopathy in the right eye with a late appearance of a choroidal neovascularization. The best-corrected visual acuity was 20/125 and 20/20 in the right and left eye, respectively. Dilated fundus examination, fluorescein angiography, and indocyanine green angiography confirmed a large subretinal fibrosis corresponding to the evolution of the choroidal neovascularization in the right eye. Spectral-domain optical coherence tomography clearly demonstrated in the right eye a large choroidal excavation below the fibrotic neovascular lesion with multiple hyperreflective foci inside the cavity, and in the left eye, a conforming focal choroidal excavation, bowl-shape type, associated with increased choroidal thickness with pachyvessels. CONCLUSION: Large choroidal excavation has been rarely reported. Although the pathogenetic mechanisms leading to the formation of large choroidal excavation are still only hypotheses, a combination of primary degenerative inflammatory factors sustaining the focal choroidal excavation formation and disruptive process of the choroidal neovascularization could be retained responsible for the large choroidal excavation.

Structural and optical coherence tomography angiography in myopic choroidal neovascularization: Agreement with conventional fluorescein angiography.

PURPOSE: To evaluate the agreement between fluorescein angiography and structural optical coherence tomography in diagnosing and monitoring the activity of myopic choroidal neovascularization and to provide a comparative analysis with optical coherence tomography angiography. METHODS: Thirteen patients with active myopic choroidal neovascularization were prospectively enrolled. At the baseline, 2-month, and 6-month visits, each patient underwent a complete ophthalmological examination, including best-corrected visual acuity assessment, fundus examination, fluorescein angiography, and optical coherence tomography with structural and angiographic assessment. Sensitivity and specificity for all optical coherence tomography parameters were evaluated taking fluorescein angiography as the reference examination. RESULTS: At the baseline, fluorescein angiography confirmed myopic choroidal neovascularization leakage in all patients. Structural optical coherence tomography demonstrated intraretinal or subretinal fluid in 61% of cases, fuzzy borders and absence of external limiting membrane visibility in 84% of cases, and subretinal hyperreflective exudation in 53% of cases. Sensitivity to the presence of retinal fluid and subretinal hyperreflective exudation was lower than sensitivity to fuzzy borders and external limiting membrane visibility, which reached 84%. During ranibizumab therapy, external limiting membrane visibility showed a higher sensitivity (100%) compared with fuzzy borders and subretinal hyperreflective exudation (66.6%) while displaying an equal specificity of 100%. At baseline and final visit, sensitivity increased to 100% when all structural optical coherence tomography parameters were pooled. Optical coherence tomography angiography detected myopic choroidal neovascularization at baseline, 2-month, and 6-month visits in 92%, 76%, and 76% of cases, respectively. CONCLUSION: The study confirms that the new indicators of myopic choroidal neovascularization activity are more reliable than the presence or absence of retinal fluid. Optical coherence tomography angiography identified myopic choroidal neovascularization in most patients in the diagnostic phase and during treatment monitoring and could be considered as an alternative to fluorescein angiography in selected patients.

Swept-source optical coherence tomography angiography vitreo-retinal segmentation in proliferative diabetic retinopathy.

PURPOSE: To identify a new cortical vitreous segmentation protocol for non invasive standardised investigation of Neovascularisation (NV) with detection of regression of NV activity in Proliferative Diabetic Retinopathy (PDR). DESIGN: Retrospective study. PARTICIPANTS: One hundred and eighty-six eyes of 93 consecutive diabetic patients (mean age: 52.6 ± 11.0 years) imaged using Topcon Triton® Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) from June 2015 to January 2017. METHODS: Scans were performed through the macula, optic disc and areas of possible NV in mid-peripheral retina using 6 × 6 mm and/or 9 × 9 mm raster-patterns in three segmentation protocols: Vitreo-Retinal (VRS), Outer-Vitreous (OVS) and Core-Vitreous Segmentation (CVS). Any suspicion of PDR was confirmed in all patients by Heidelberg® Widefield-Fundus-Fluorescein-Angiography (WF-FFA) and/or Optos® Ultra-WF-FFA (UWF-FFA). Inter-observer reproducibility of NV diagnosis and agreement between SS-OCTA and UWF-FFA were assessed. Primary outcome was the identification of an effective and reproducible segmentation protocol. Secondary outcome was the identification of NV regression after treatment. RESULTS: Sensitivity-specificity reached, respectively, the value of 100 to 100 in detecting NVD, and 96.6 to 100 in detecting NVE in compared areas. SS-OCTA was able to confirm absence of blood flow within the residual NV plexus when using VRS protocol in 30 eyes in which regression of NV with absence of leakage was documented on FFA. CONCLUSION: Three segmentation protocols (VRS, OVS and CVS) with different but complementary characteristics, allowed a reproducible and standardised investigation of NVD and NVE. The proposed new SS-OCTA cortical vitreous segmentation protocols may be of value when identifying and assessing NV-activity (VRS, OVS and CVS) or NV-regression (VRS) in PDR and therefore, response to therapy.

Photodynamic Therapy with Verteporfin for Chronic Central Serous Chorioretinopathy: A Review of Data and Efficacy.

Central serous chorioretinopathy represents the fourth most frequent retinal disorder, occurring especially in young age. Central serous chorioretinopathy is mainly characterized by macular serous retinal detachment and although the clinical course moves frequently toward a spontaneous resolution, the subretinal fluid may persist for a long time, thus evolving to the chronic form, and leading to a potential damage of the retinal pigment epithelium and to photoreceptors. The photodynamic therapy with verteporfin plays an important role in the armamentarium among the many therapeutic options employed in this complex retinal disorder. In this review, the authors aim to summarize data of efficacy and safety of PDT focusing especially on mechanisms of action of the PDT and providing comparative outcomes with the alternative therapeutic approaches, including especially the subthreshold laser treatment.

Central Serous Chorioretinopathy: Treatment with Laser.

Currently, no general consensus exists regarding the management of central serous chorioretinopathy (CSC). Laser treatments include three different therapeutic approaches: conventional laser, subthreshold laser and photodynamic therapy. Conventional focal laser, addressed to seal the leaking points, as evidenced on fluorescein angiography, was largely used in the past, but now, it is almost completely abandoned, owing to the potential complications. Several studies confirmed the positive effects achieved by subthreshold laser treatment in CSC, even though its improper application in the PLACE trial has questioned the effectiveness.

Anti-VEGF and Retinal Dystrophies.

The therapeutic approach based on anti-vascular endothelial growth factor (anti-VEGF) molecules can be used to treat two important complications of retinal dystrophies: choroidal neovascularization and macular edema. The macular involvement in retinal dystrophies can lead to further visual deterioration in patients at a young age and already affected by functional limitations. The study reports the effect of anti-VEGF treatment in several subforms of retinal dystrophies, critically discussing advantages and limitations.

Microvasculature Changes of Myopic Choroidal Neovascularization and the Predictive Value of Feeder Vessel Disappearance after Ranibizumab Treatment Revealed Using Optical Coherence Tomography Angiography.

AIM: To investigate vascular changes of myopic choroidal neovascularization (mCNV) after ranibizumab treatment using optical coherence tomography-angiography (OCTA). METHODS: Consecutive subjects with a diagnosis of mCNV were included. Patients underwent intravitreal injection of ranibizumab treatment with a 6-month follow-up. All patients underwent a complete ophthalmological examination and OCTA evaluation. The 3 × 3 OCTA en face images were analyzed for the absence/presence of mCNV, CNV area, and CNV network morphology. In particular, the morphology of the mCNV was analyzed in order to detect the presence/absence of feeder vessels. RESULTS: Eleven subjects were evaluated. At baseline, the mCNV was identified in all cases on OCTA. At 6 months, the mean mCNV area was not statically significantly reduced in comparison with baseline values (p > 0.05), while the morphologic analysis revealed a complete disappearance of the feeder vessel in 6 eyes. The subgroup analysis of these latter showed that the CNV area was significantly reduced, visual acuity had improved, and only one intravitreal injection was administrated over the entire follow-up period. CONCLUSIONS: OCTA allowed the detection of qualitative and quantitative vascular changes in mCNV. The disappearance of the feeder vessel was associated with better anatomical as well as functional outcomes at the last follow-up visit.

Large choroidal excavation in retinitis pigmentosa: A case report.

PURPOSE: To report the morphological and clinical features of a case of retinitis pigmentosa with large choroidal excavation. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity assessment, anterior segment and dilated fundus examination and spectral-domain optical coherence tomography. RESULTS: A 41-year-old woman affected by retinitis pigmentosa with genetic confirmation with mutation in RDH12 gene had a best-corrected visual acuity of 20/50 in both eyes. Dilated fundus examination revealed waxy pallor of the optic disc, diffuse narrowing of the retinal arterioles and a generalized retinal pigment epithelium mottling with bony spicule associated with diffuse retinal atrophy. At the posterior pole, an extended bilateral chorioretinal atrophy was evident with a partial sparing of the macular area. On spectral-domain optical coherence tomography, a bilateral large choroidal excavation could be clearly detected and it was associated with a diffuse retinal thinning at the posterior pole and a partial sparing of the fovea. CONCLUSION: Large choroidal excavation has been rarely reported. Although the pathogenetic mechanisms leading to the formation of large choroidal excavation are still a matter of debate, a combination of primary degenerative-inflammatory factors could be retained responsible for the large choroidal excavation development.

Near-infrared fundus autofluorescence in early age-related macular degeneration.

PURPOSE: To describe the patterns on near-infrared fundus autofluorescence in eyes affected by early age-related macular degeneration. DESIGN: Cross-sectional observational case series. PARTICIPANTS: A total of 84 eyes of 84 patients suffering from early age-related macular degeneration (>63 µm but <125 µm drusen and no-to-mild retinal pigment epithelium abnormalities) were enrolled. METHODS: Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence, and near-infrared fundus autofluorescence. Eyes were classified according to different patterns of near-infrared fundus autofluorescence. Main outcome was definition of relative prevalence and features of each near-infrared fundus autofluorescence pattern; secondary outcomes were correlation between near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence and between near-infrared fundus autofluorescence patterns and best-corrected visual acuity. RESULTS: Four different patterns of near-infrared fundus autofluorescence identified: normal foveal signal (Pattern A, 7%); normal foveal signal with hyperautofluorescent/hypoautofluorescent spots not involving the fovea (Pattern B, 65.5%); hyperautofluorescent/hypoautofluorescent spots involving the fovea (Pattern C, 15.5%); patchy pattern (Pattern D, 12%). best-corrected visual acuity was lower in eyes with foveal signal alteration (Patterns C and D). CONCLUSION: Near-infrared fundus autofluorescence pattern in early age-related macular degeneration might be suggestive of visual function deterioration when the fovea is involved. Longitudinal studies are warranted to confirm our preliminary results.

CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Early and Late Morphological and Functional Changes After Verteporfin Photodynamic Therapy.

PURPOSE: To describe early and late morphological and functional changes in subjects receiving photodynamic therapy (PDT) for chronic central serous chorioretinopathy. METHODS: Patients with chronic central serous chorioretinopathy were prospectively enrolled and received standard PDT. At the baseline examination, each subject underwent complete ophthalmological examination, including best-corrected visual acuity (BCVA) assessment, fluorescein angiography and indocyanine green angiography, spectral domain optical coherence tomography, and microperimetry. Spectral domain optical coherence tomography, microperimetry, and BCVA assessment were repeated in multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals. Main outcome measures were: identification of early changes (1-week examination) in BCVA, retinal sensitivity, and spectral domain optical coherence tomography parameters and their influence on outcomes at the 1-year follow-up. RESULTS: Three main patterns of early response to PDT were identified during the 1-week examination. The neurosensory retinal detachment most frequently decreased rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in neurosensory retinal detachment height was registered in 16% (3/19) of cases, whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was encountered. Best-corrected visual acuity declined significantly in 5/12 patients in the first group and was stable or improved in the remaining cases. Overall, retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56 dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4 letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment completely resolved in 18/19 (95%) cases, with a parallel significant reduction in central foveal choroidal thickness (P < 0.0001). CONCLUSION: Three patterns of early response to standard PDT can be identified. Although an early and abrupt reduction in BCVA and retinal sensitivity after treatment is possible, this does not compromise a final improvement in visual functions.

Fluorescein Leakage and Optical Coherence Tomography Features of Choroidal Neovascularization Secondary to Pathologic Myopia.

Purpose: We compare the fluorescein angiography (FA) patterns with morphologic alterations detectable on spectral-domain OCT (SD-OCT) in myopic choroidal neovascularization (mCNV) and evaluate whether they influence the effects of intravitreal ranibizumab (IVRI) in an as-needed (PRN) regimen. Methods: The 49 patients enrolled in this prospective case series underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), FA, and SD-OCT assessment. The main outcome measure was correlation between FA patterns and SD-OCT features. Secondary outcomes were changes in BCVA and central macular thickness (CMT), and characterization of subretinal hyperreflective exudation (SHE). Results: Three main patterns were identified on the FA: no (5%), minimal (35%), and profuse (59%) leakage CNV. Comparison between minimal versus profuse leakage CNV subtypes revealed no difference regarding baseline and final BCVA, CNV area, choroidal thickness, final CMT, and proportion of intraretinal cysts, subretinal fluid, and external limiting membrane (ELM) interruption; however, the minimal leakage CNV subgroup revealed a lower percentage of SHE (P = 0.0039), required fewer IVRI (P = 0.003), and showed a baseline smaller CMT (P = 0.004). Patients presenting with SHE showed a similar baseline BCVA to those without exudation, but displayed greater final BCVA improvement. CMT was greater at the baseline and the reduction also was more marked. CNV area achieved a significant reduction only in eyes with SHE. ELM interruption was present in all cases compared to 86.3% of eyes without SHE. Lastly, the eyes with SHE required more injections (P = 0.04). Conclusions: Different patterns of mCNV may be identified in FA and they correlate with specific SD-OCT alterations. Moreover, the type of FA leakage may assist in identifying more active mCNV.

A Pathogenetic Classification of Diabetic Macular Edema.

PURPOSE: The aim of this study was to define a new pathogenetic classification of diabetic macular edema (DME) and to present the results of its application in common clinical practice. METHODS: One hundred and seventy-seven consecutive patients with center-involving DME, central retinal thickness (CRT) ≥250 µm, were prospectively enrolled. A complete ophthalmological examination included best-corrected visual acuity (BCVA) assessment, fundus photography, and spectral-domain optical coherence tomography (OCT). The DME classification was broken down into 4 categories, combining the presence of retinal thickening with the presence/absence of visible vascular dilations and OCT-detectable macular traction. The OCT parameters included were as follows: CRT, subretinal fluid, intraretinal cysts, and hyper- reflective foci (HF). RESULTS: Four subtypes of DME were identified: vasogenic (131 eyes, DME with vascular dilation), nonvasogenic (46 eyes, DME without vascular dilation), tractional (11 eyes), and mixed DME (13 eyes). Vasogenic DME was the pattern mainly represented in each subclass of CRT (< 300, 300-400, and > 400 µm), with tractional DME observed especially with CRT > 400 µm. Internal and external cysts and a greater presence of hard exudates were predominantly found in vasogenic DME, whereas HF was equally distributed in the 4 DME subgroups. CONCLUSION: The study offers a new pathogenetic classification able to detect significant differences among DME subtypes. A tailored therapeutic approach could take into consideration specific changes associated with the different DME subtypes.

MICROPERIMETRY IN BEST VITELLIFORM MACULAR DYSTROPHY.

PURPOSE: To investigate retinal sensitivity in eyes with all the clinical stages of Best vitelliform macular dystrophy (VMD). METHODS: Thirty-two patients affected by VMD in subclinical, vitelliform, pseudohypopyon, vitelliruptive, and atrophic stages were enrolled in this prospective cross-sectional study. Patients underwent a complete ophthalmologic examination, including determination of best-corrected visual acuity (BCVA), staging of the disease (Gass's classification), and microperimetry by means of the macular integrity assessment microperimeter. The primary outcome measure was to describe the alterations in the retinal sensitivity of eyes affected by VMD in different stages. Secondary outcome measures included correlations between retinal sensitivity and best-corrected visual acuity and the correlation between the VMD stage and the specific microperimetry pattern. RESULTS: Mean retinal sensitivity was reduced in all the VMD stages. Nevertheless, vitelliform, pseudohypopyon, and vitelliruptive stages turned out to be very similar, especially within 10°. Fixation was classified as stable in 27 eyes (44.2%), relatively unstable in 16 eyes (26.2%), and unstable in 18 eyes (29.5%). Fixation stability correlated both with the disease stage and best-corrected visual acuity. CONCLUSION: VMD is characterized by complex microperimetric abnormalities, involving the whole macular area. Microperimetry may contribute to the global clinical assessment of patients affected by VMD and could be used in future therapeutic approaches.