Dark halo, a new biomarker in macular neovascularization: comparison between OCT angiography and ICGA-a pilot prospective study.

PURPOSE: To compare optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) in terms of reliability in detecting dark halo in patients affected by age-related macular degeneration (AMD) complicated with type 1 macular neovascularization (MNV). METHODS: Eighty-nine eyes of 89 patients were analyzed at the University of Naples Federico II between January 2018 and October 2021. Each patient underwent a complete ophthalmological evaluation including fluorescein angiography, ICGA, spectral domain optical coherence tomography (SD-OCT), and OCTA. OCTA and ICGA images of dark halo were compared. The paired Student's test and intraclass correlation coefficients were used to evaluate the differences in dark halo measurements between OCTA and ICGA images. RESULTS: Thirty-six eyes of 36 patients were included in this prospective study. Dark halo area was significantly larger in OCTA than in ICGA (1.49 ± 1.8 mm2 vs. 0.54 ± 0.5 mm2; p = 0.001). Moreover, the agreement between the two types of devices for measuring dark halo areas was poor, with a low intraclass coefficient correlation (0.397). CONCLUSION: OCTA could be a useful and necessary tool to investigate dark halo in neovascular AMD due to its ability to visualize the areas of reduced vessel density around MNV in greater detail compared to ICGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05108285.

The role of quantitative deep capillary plexus in the pathogenesis of type 3 macular neovascularization: an optical coherence tomography angiography study.

PURPOSE: To quantitatively investigate the role of deep capillary plexus (DCP) in patients affected by type 3 macular neovascularization (MNV), compared to patients with reticular pseudodrusen (RPD) eyes and healthy controls, using optical coherence tomography angiography (OCTA). METHODS: In this prospective observational study, a total of seventy-eight eyes of 78 patients were included. Group 1 consisted of 40 eyes of 40 patients with stage 1 of type 3 MNV (22 males, 18 females, mean age 73.7, SD ± 6.60) and group 2 included 38 eyes of 38 patients with RPD (17 males, 21 females, mean age 73.2, SD ± 4.55). The control group included 40 eyes of 40 healthy subjects (20 males, 20 females, mean age 71.4, SD ± 6.36 years). We evaluated the retinal vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) using OCTA. RESULTS: Patients with diagnosis of type 3 MNV showed statistically lower values of VD in DCP with respect to controls and to RPD group (p < 0.001), while there were no statistical differences between RPD and control group in macular region. No significant differences in VD of SCP were detected among the three study groups. CONCLUSION: OCTA provides a reproducible, non-invasive detailed quantitative analysis of retinal vascular features and changing in early-stage type 3 MNV patients, which allowed to shed the light on the main role of DCP ischemia in the development of type 3 MNV.

Conjunctival Carcinomas Arising in the Anophthalmic Socket.

PURPOSE: The aim of this study was to report management and outcomes of patients in which conjunctival carcinomas arose in the anophthalmic socket. METHODS: The authors retrospectively analyzed the data of patients which presented the anophthalmic socket after surgery. The clinical records of 4 patients with histological diagnosis of conjunctival carcinoma in the anophthalmic socket, referred to our Department, between January 2014 and December 2019 was collected. RESULTS: The study included 4 men (median age 58 years). A previous enucleation surgery had been performed in all patients due to previous ocular trauma for three patients (Case 1, 3, and 4) and due to a retinoblastoma for 1 patient (Case 2). All patients underwent surgical excision of the lesion and only 1 patient (case 3) underwent orbital exenteration due to the high-grade of the cancer. The most common tumor was the squamous cell carcinoma (2 cases) followed by 1 case of high-grade mucoepidermoid carcinoma and 1 case of carcinoma in situ. Systemic work-up was performed for all the patients. Conjunctival TNM, according to the American Joint Committee on Cancer TNM staging system was used to stage the lesions. The median follow-up time was 15 months. CONCLUSION: Considering the severity and rarity of these tumors, a careful ophthalmological examination of the cavity and a correct revision of the prosthesis should be mandatory in order to ensure the elimination of any macro and microscopic irregularities that can then in the long-term cause chronic inflammation of the tissues and consequently promote the growth of carcinomas.

Primary cutaneous anaplastic large-cell lymphoma of the eyelid: report of two cases and review of the literature.

PURPOSE: Two new cases of primary cutaneous CD30+ anaplastic large-cell lymphoma (cALCL) of the eyelid are reported; these are analysed alongside existing cases to identify challenges relating to the diagnosis and management of such rare lesions. MATERIAL AND METHODS: A review of existing literature on the PubMed database is conducted using the keywords: 'eyelid lymphoid proliferations', 'lymphoma of the eyelid', and 'primary cutaneous CD30+, ALK-anaplastic large-cell lymphoma of the eyelid'. Two new cases of cALCL are reported. Cases where patients present solely with a nodular periocular lesion are analysed for recurrence and survival rate. RESULTS: Two new patients with a painless ulcerated nodule on the upper eyelid receive a confirmed diagnosis of cALCL after undergoing an excisional biopsy. The first, elderly patient has spontaneous remission; the second patient, with a concomitant chronic infection of hepatitis C virus (HCV), presents a more diffuse disease at the onset and requires radiotherapy. Together with 13 patients a primary cALCL identified from 11 previous studies, this constitutes a cohort of 15 patients. Of these, 10 present with an exclusively nodular lesion of the eyelid and four experience disease recurrence; no deaths from cALCL are reported. CONCLUSION: Differential diagnosis between primary cALCL and lymphomatoid papulosis is essential and requires careful consideration of clinical and pathologic features. Radiologic staging examination is crucial in order to exclude systemic ALCL, particularly for patients with comorbidity. Though cALCL has the pathological features of a malignant lesion, the prognosis seems favourable for patients; a relatively high percentage even experience spontaneous resolution.

Epidemiological Analysis of Venous Malformation of the Orbit.

Orbital venous malformation (OVM) is one of the most common orbital mass of adults, accounting for approximately 5% to 15% of all vascular abnormalities in the central nervous system and representing 9% of orbital lesions. Clinical presentation is variable from asymptomatic cases to symptomatic ones. The purpose of the authors' work is to analyze OVM incidence and prevalence in a cohort of patients referred over the last 40 years to the Orbital Unit, tertiary center for orbital diseases.Records of 224 patients diagnosed with CVM in a 40-year period were retrospectively reviewed extracting prevalence/year and incidence/year based on data obtained from Eurostat population statistics. Data were aggregate and analyzed with a Microsoft Excel (Microsoft Corporation, Redmond, WA) spread sheet.The incidence rate was measured as the number of new cases of OVM observed in Orbital Unit, a tertiary center. Incidence was about 1 case out (0.94) every 10 million people. The incidence rate was measured also as the number of new cases of OVM observed in Campania, considering in the latter case patients residents in this region (112 patients). Incidence was less than 1 case out (0.58) every 10 million people.The prevalence rate was measured as the proportion of individuals with OVM observed in our Orbital Unit and is equal to 5%. This indicator resulted to increase from 1977 to 2017.The management of OVM is still under discussion, but in agreement with data present in the literature the authors still believe that the surgical indication is only for symptomatic lesions.

The Relationship between Macular Pigment and Vessel Density in Patients with Type 1 Diabetes Mellitus.

AIM: Macular pigment density and microvascular density on optical coherence tomography angiography (OCTA) were measured in a cohort of type 1 diabetes mellitus (T1DM) patients with retinopathy in the attempt to shed light on the pathophysiology of this condition. METHODS: Eighty-two consecutive eyes of 59 patients with diabetic retinopathy examined at the Eye Clinic of the University of Naples Federico II from November 2016 to April 2017 were enrolled in this prospective study. Eighty normal eyes of 40 age-matched subjects without diabetes mellitus, without a history of glaucoma or evidence of intraocular surgery, and without retinal pathologic features constituted the control group. All patients and controls underwent a complete ophthalmic examination, best corrected visual acuity evaluation according to the ETDRS visual logMAR scale, measurement of intraocular pressure, OCTA, and evaluation of macular pigment. RESULTS: There were no significant age differences between patients and controls. Both macular pigment measurements and vessel density measured by OCTA were significantly lower in patients than in controls. A moderate correlation was found between vessel density in all ETDRS sectors and macular pigment parameters. CONCLUSIONS: There was a reduction in macular pigment and in OCTA vessel density in T1DM patients with retinopathy, which may have prognostic value in determining disease progression.

A case series of Merkel cell carcinoma of the eyelid: a rare entity often misdiagnosed.

Merkel cell carcinoma (MCC) is one of the rarest eyelid tumors, with high mortality rate due to lymphatic and metastatic spread. We hereby report six cases of patients with histological diagnosis of MCC referred to our Orbit Unit between 2012 and 2018, focusing on diagnosis, treatment, and subsequent follow up. All patients underwent surgical excision and systemic work-up. Both MCC TNM and eyelid MCC TNM were used to stage lesions. MCC of the eyelid is usually misdiagnosed as benign or other malignant lesions. A prompt examination and a wide local excision are mandatory. A close follow-up of these patients is advised due to high recurrence rate and lymphatic spread.

Structural and clinical changes in previously treated type 1 macular neovascularization in non-responder AMD eyes switched to brolucizumab.

PURPOSE: To examine structural and clinical changes in previously treated type 1 macular neovascularization (MNV) in non-responder age-related macular degeneration (nAMD) eyes switched to brolucizumab. Subretinal hyper-reflective material (SHRM), intraretinal (IRF) and subretinal fluid (SRF) presence, fibrovascular-pigment epithelium detachment (PED) height and central macular thickness (CMT) variation were analyzed using optical coherence tomography (OCT). METHODS: In this prospective study all patients underwent a complete ophthalmological evaluation including structural OCT at baseline (T0), one month (T1), three (T2), four (T3) and six months after switching to brolucizumab treatment (T4). Non-responder criterion was the persistence of IRF and SRF. Moreover, CMT and BCVA had shown worsening or no improvement before switching to brolucizumab. Clinical function and structural activity biomarkers were measured at each visit and changes were analyzed. P value <0.05 was considered statistically significant. RESULTS: Twenty eyes of twenty patients were enrolled. All the structural variables examined during the follow-up showed significant reductions. Decreases in IRF, SRF and PED were already significant at T1 (p < 0.05). SHRM was significantly reduced at T2 (p < 0.05). Structural biomarkers were absent at T3. At T4, all biomarkers remained stable while SHRM was no longer detectable in 18 patients. Changes in visual acuity from baseline to T4 were not significant. CONCLUSION: This short-term experience highlights that brolucizumab might be considered an effective treatment option in nAMD with type 1 MNV, as it can promote a reduction of structural activity biomarkers.

A rare case of simultaneous occurrence of non-arteritic anterior ischemic optic neuropathy and corpus callosum ischemia.

PURPOSE: To report a case of non-arteritic anterior ischemic optic neuropathy (NAION) in an elderly patient with ischemia of the left splenium of the corpus callosum, providing details of the diagnostic work-up and subsequent follow-up. METHODS SECTION: Case report. RESULTS: A pseudophakic 80 years-old woman referred complaining sudden visual impairment in the left eye (LE) in concomitance with episode of hypertensive crisis. Fundus examination showed diffuse swelling of optic disc associated with flame peripapillary hemorrhages in LE and small crowded disc in right eye (RE). A superior altitudinal defect with arcuate defect including the blind spot were detected at the visual field in the LE. The patient was diagnosed with NAION. Five days later the patient complained a further vision loss and a pathological area within the left splenium of corpus callosum, consistent ischemia, was depicted at magnetic resonance imaging of brain. Corpus callosum infarction was completely asymptomatic and neurological evaluation was normal. At 45 days follow-up fundus examination showed white ischemic nerve while visual field was irreversibly constricted with tubular defect in LE. CONCLUSION: In case of NAION linked with corpus callosum ischemia multimodal imaging and systemic work-up play a pivotal role for an early diagnosis.

Pathogenesis of Central Serous ChorioRetinopathy and the Link between Choroidal Hyperpermeability and RPE Pump Reversal.

PURPOSE: To describe 6 cases of acute central serous chorioretinopathy (CSCR) and the response to laser treatment, focusing on the underlying pathogenic mechanism. METHODS: Multimodal imaging from 6 eyes of 6 patients with acute and recurrent CSCR were reviewed including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) at baseline and after laser therapy. RESULTS: In 3 out of the 6 cases with acute CSCR, the hyporeflective lucency sign was identified with cross sectional and en face OCT and co-localized with an intense active inkblot retinal pigment epithelium (RPE) leak on FA. The development of this sign was suggestive of active leakage into the subretinal space displacing overlying subretinal hyperreflective material (SHRM) and suggestive of a reversal of RPE pump function. All six cases were treated with focal laser to directly target the intense leakage points with remarkable resolution of the fluid due to destruction of the RPE cells mediating reversal of pump function. CONCLUSIONS: Unlike chronic CSCR in which degenerative changes of the RPE lead to oozing of fluid into the subretinal space, in acute forms of CSCR including bullous CSCR, there are focal leaks of the RPE that actively drive fluid into the subretinal space suggestive of RPE pump reversal. We propose that pachychoroid disease causes increased hydrostatic pressure and increased resistance to the RPE pump thereby triggering a reversal in pump function. Understanding this concept can have therapeutic implications.

Management of presumed candida endophthalmitis during the COVID-19 pandemic: Case report and review of the literature.

PURPOSE: To report the management of a case of candida endophthalmitis following intubation for SARS-CoV-2 ARDS, during the first lockdown, underlining consequently the limited access to the gold standard of care. METHODS: Case report. RESULTS: We have described the case of a 56-year-old Hispanic man who developed bilateral Candida endophthalmitis after one month of hospitalization in the intensive care unit for severe SARS-CoV-2 pneumonia. Multimodal imaging was obtained. Full serological screening for infection was done resulting negative. A diagnostic vitrectomy was impossible due to the limited access at the surgery room. Diagnosis of presumed candida endophthalmitis was made, according to a highly qualified center, and therapy with intravenous liposomal amphotericin B was administered. At three months, we observed lack of vitreous opacities and atrophic scars with no active lesions. CONCLUSIONS: Diagnosis of candida endophthalmitis was a challenge in this pandemic scenario, given the impossibility of performing a diagnostic vitrectomy. Therefore, it was mainly based on patient's clinical manifestations, multimodal imaging and on unanimity of collegiality between our hospital and the highly specialized center.

Spontaneous closure of full-thickness macular hole after pars plana vitrectomy for retinal detachment: evidence of ellipsoid zone restoration.

PURPOSE: To describe a case of full-thickness macular hole (FTMH) occurred after pars plana vitrectomy (PPV) for a macula-sparing rhegmatogenous retinal detachment (RRD), which showed a spontaneous closure associated with outer retinal layers restoration. METHODS: Case report. RESULTS: A pseudophakic 69-year-old man underwent PPV for a macula-sparing superior RRD in the right eye (RE). Best corrected visual acuity (BCVA) was 20/20 before surgery. Three weeks after treatment the patient complained about visual impairment, and a FTMH was detected at fundus examination as well as confirmed by optical coherence tomography (OCT) scan. The patient was scheduled for a repeated surgery, but FTMH spontaneously closed eighteen days after its occurrence as demonstrated at OCT showing only a point break of the ellipsoid zone (EZ) and Verhoeff membrane. The subsequent macular OCT scan showed a point-like irregularity at the Verhoeff membrane and regeneration of EZ, associated with a progressive improvement in BCVA. Forty-days after the FTMH occurrence, all the retinal layers were completely restored with a complete clinical recovery. CONCLUSION: FTMH formation and closure after macula-sparing RRD repair is a rare event that could be characterized by spontaneous and gradual anatomical restoration of the EZ associated with visual acuity improvement, underlying the retinal physiology recovery.

Structural and vascular features in cavitary congenital optic disc anomaly associated with metaphyseal acroscyphodysplasia.

PURPOSE: To evaluate the radial peripapillary vascular plexus of a cavitary congenital optic disc anomaly in a young patient with recessive autosomal metaphyseal acroscyphodysplasia using optical coherence tomography angiography (OCTA). METHODS: Observational case report. RESULTS: A 17-year-old man, with diagnosis of metaphyseal acroscyphodysplasia was referred to Eye Clinic for fundus examination and multimodal imaging for retinal epithelium hypertrophy in the right eye. Clinical examination showed cup-shaped metaphyses, short stature, hyperthelorism, and telecanthus. An optic disc coloboma was detected in the right eye on fundus examination. Wide field en-face Optical Coherence Tomography (OCT) showed a hyporeflective area corresponding to the right optic disc coloboma. At OCTA examination, the whole papillary region revealed a rarefaction of the vascular network, while the ganglion cell complex's and retinal fiber layers' parameters were normal in both eyes. CONCLUSION: The presence of coloboma disc congenital defect linked to embryological abnormalities during the development process could pave the way for a wider understanding of the pathogenesis of metaphyseal acroscyphodysplasia by increasingly framing it as a systemic disease.

OCTA in macular intraretinal microvascular abnormalities: Retinal vascular density remodeling after panretinal photocoagulation.

PURPOSE: To describe a case of macular intraretinal microvascular abnormality (IRMA) detected with Optical Coherence Tomography Angiography (OCTA) and to show its remodeling and vascular density changes after panretinal photocoagulation (PRP) during an 18-month follow-up. METHODS: Case report. RESULTS: A 22-year-old female patient with proliferative diabetic retinopathy was found to have a small hyperreflective formation with posterior shadow cone and signal flow, located at the temporal margin of the fovea avascular zone (FAZ), identified as macular IRMA with OCTA. Her best-corrected-visual acuity was 20/20. Four months later the macular IRMA was larger and, in its context, there was also an increase in the flow area in B-scan. The patient underwent PRP and after 18 months we observed a regression of macular IRMA and an increase in the superficial capillary plexus vessel density in all sectors in comparison to baseline. CONCLUSION: OCTA is a non-invasive tool that recognize macular IRMA in diabetic retinopathy patient and it could be helpful to follow their qualitative and quantitative vascular evolution over time.

Diffuse posterior scleritis associated with HLA-B14* managed with multimodal imaging: case report and review of the literature.

PURPOSE: To report a case of posterior scleritis (PS) in an HLA-B*14 positive patient highlighting the crucial role of multimodal imaging and of autoimmune systemic disease screening for the diagnosis. METHODS: Case Report. RESULTS: A 73-year-old woman, complaining of ocular discomfort in right eye (RE), presented conjunctival hyperemia, keratic precipitates involving the anterior segment and four chorioretinal elevations with macular folds at fundus examination. Multimodal imaging and systemic diagnostic work-up were performed. While awaiting results, topical corticosteroid was prescribed. Four days later, worsening of exudative chorioretinal was detected. Except for erythrocyte sedimentation rate, tests were negative, while molecular typing of HLA genes was positive for HLA-B*14. Diagnosis of PS was confirmed by ultrasound examination while diagnosis of ankylosing spondylitis was made by rheumatologist. The patient was given systemic corticosteroid and one month later the posterior segment was unremarkable. CONCLUSION: HLA-B*14 may configure as a causal factor so autoimmune systemic disease screening should rule this out in management of PS, which should be diagnosed on the basis of multimodal imaging.

OCT-A in chronic central serous chorioretinopathy treated with oral eplerenone and half-fluence photodynamic therapy: A comparative study.

PURPOSE: To evaluate retinal and choriocapillary vessel density (VD) changes in patients with chronic central serous chorioretinopathy (CSC) treated with half-fluence verteporfin photodynamic therapy (vPDT) or eplerenone, using optical coherence tomography angiography (OCTA). METHODS: Patients affected by CSC and treated with vPDT and eplerenone were retrospectively studied. At baseline and 3 months after each treatment, all patients underwent a complete ophthalmological examination, including an evaluation of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain optical coherence tomography (SD-OCT) and OCTA. RESULTS: Forty-eight eyes of patients with CSC were analysed. Twenty-four eyes were placed in the vPDT group, and 24 eyes formed the eplerenone group. In both groups, OCTA showed a significant improvement in the VD of deep capillary plexus (DCP) and choriocapillaris (CC) after treatments with respect to baseline (p < 0.001), whereas the VD of superficial capillary plexus (SCP) did not show significant differences (p > 0.05). The PDT group demonstrated a statistically significant increase in the VD of DCP and CC with respect to the eplerenone group (DCP p = 0.012; CC p = 0.004). A statistically significant reduction with respect to baseline in subfoveal choroidal thickness (SFCT) (p = 0.001 for vPDT group; p = 0.001 for eplerenone group) and in central foveal thickness (CFT) (p = 0.001 for vPDT group; p = 0.001 for eplerenone group) was also found. The SFCT was significantly thinnest in the PDT group with respect to the eplerenone group (p = 0.021). CONCLUSION: OCTA allowed us to study retinal and choriocapillary vascular changes in patients with CSC treated with vPDT and eplerenone.

Recurrence of Exophthalmos after 10 Years from Orbital Floor Decompression for Dysthyroid Orbitopathy: A Case Report.

Dysthyroid orbitopathy or Graves' ophthalmopathy (GO) is an autoimmune disease with a complex pathogenesis that usually occur in patients with hyperthyroidism. Surgical decompression of the orbit is an accepted and validated treatment of thyroid eye disease (TED). This is a case of a patient with left exophthalmos and ipsilateral maxillary sinusitis after 10 years from the surgical bone decompression of the orbital floor for TED.

Macular hemorrhage after laser exposure and cannabinoid intake during a disco party.

PURPOSE: To describe two cases of macular hemorrhage in young patients, both occurred after laser exposure and cannabinoid intake during a disco party. OBSERVATIONS: Case 1: a 21-year-old man was evaluated at our Emergency Unit for sudden vision loss in the right eye (RE). Best-corrected visual acuity (BCVA) was count fingers in the RE and 20/20 in the left eye (LE). Fundus examination revealed a broad pre-retinal hemorrhage in macular region of RE, confirmed by optical coherence tomography. The patient reported vision loss, suddenly occurred after fixation of a laser source and cannabinoid intake during a disco party the night before. We administered a macular supplement and closely followed up the patient. After two months BCVA of the right eye was 20/20. CASE 2: The following day another 21-year-old man was referred to our Emergency Unit complaining of sudden vision loss in LE. As in Case 1, he reported to have fixed a laser beam as well as the consumption of cannabinoids at the same disco. BCVA was count fingers in the LE and 20/20 in the RE. Fundus examination showed a broad pre-retinal hemorrhage in macular region of LE. He had taken the macular supplement for two months and then the hemorrhage was reabsorbed. CONCLUSION AND IMPORTANCE: Laser exposure must be considered as a possible cause of macular hemorrhage. Furthermore, low cost of drugs and lack of formal control of laser sources may increase the emergence of new cases of retinal injuries especially among young people.

Evaluation of vessel density in disorganization of retinal inner layers after resolved diabetic macular edema using optical coherence tomography angiography.

PURPOSE: To evaluate the retinal vessel density (VD) in the macular region and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with and without disorganization of retinal inner layers (DRILs) after resolution of diabetic macular edema. METHODS: Thirty-seven eyes of 37 DRIL patients (mean age 63 ± 13.97 years), 30 eyes of 30 no DRIL patients and 35 eyes of 35 controls were enrolled in this study. We evaluated the VD in the macular region of superficial capillary plexus (SCP), deep capillary plexus (DCP) and FAZ area. RESULTS: DRIL and no DRIL groups showed decreased VD in SCP and DCP (p<0.05) and a larger FAZ area (p<0.001) compared to controls. However, DRIL patients revealed a statistically significant reduction in VD of SCP (p = 0.041) and a greater FAZ area (p<0.001) with respect to no DRIL patients. We found a significant negative correlation between the VD of the foveal SCP (r = -0.414, p = 0.011), foveal DCP (r = -0.358, p = 0.025) and best corrected visual acuity (BCVA) in DRIL group. Moreover there was a significant positive correlation between the FAZ area (r = 0.425, p = 0.034) and BCVA. Therefore, in presence of DRILs lower VD values of SCP and DCP and a larger FAZ area correlated with a worse visual acuity. In no DRILs group, there was a significant negative correlation between the VD of the foveal DCP and BCVA. CONCLUSION: OCTA highlights the role of retinal vascular ischemia in the pathogenesis of DRILs. This parameter could represent an important functional predictive factor in diabetic patients.