Pathogenesis of Central Serous Chorioretinopathy and the Link Between Choroidal Hyperpermeability and Retinal Pigment Epithelium 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 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 6 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Anterior Segment-Optical Coherence Tomography features in Blau syndrome.

Blau syndrome (BS) is a rare granulomatous auto-inflammatory disease, characterized by the classic clinical triad of joints, skin and ocular involvements. Ocular manifestation usually consists in a bilateral insidious chronic anterior uveitis with a potential evolution to panuveitis. We describe the case of two siblings, an 8-years old female and a 5-years old male, with a diagnosis of BS, evaluated by Anterior Segment-Optical Coherence Tomography (AS-OCT). In the female patient, slit-lamp examination revealed bilateral anterior granulomatous uveitis and inflammatory sequelae. AS-OCT revealed high intensity reflective layers in the anterior cornea, hyperreflective dots both in the aqueous humor and in the posterior corneal surface. In the male, no signs of inflammation were detected both on slit-lamp examination and AS-OCT scans. AS-OCT is a valuable, non-invasive tool that could improve the diagnosis of ocular involvement, better characterize and follow-up corneal alterations and anterior segment features in pediatric patients with BS.

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.

A rare case of bilateral conjunctival Kaposi's sarcoma in a HIV-negative patient.

PURPOSE: Kaposi's sarcoma (KS) is a rare multi-centric vascular neoplasm, first described by Moritz Kaposi in 1872. It can appear in four different forms: classic, endemic, HIV-related and post-transplant form. We present an uncommon case of seronegative HIV infection patient with skin KS involving conjunctiva of both eyes. OBSERVATIONS: Firstly, right eye lesions were surgically removed. Subsequently, the patient was administered with systemic chemotherapy (doxorubicin) to treat both skin and left eye lesions. No signs of recurrence were observed at 20 months' follow-up. CONCLUSIONS: Both eyes involvement in KS is rarely described in scientific literature. Both surgery and chemotherapy could be considered valid treatment options for conjunctival KS.

Retinal Vascular Assessment in Psoriasis: A Multicenter Study.

PURPOSE: To investigate the vascular status of the macula in psoriasis patients without history of ocular inflammation by Optical Coherence Tomography Angiography (OCTA). METHODS: This prospective cross-sectional multicenter study included 55 psoriasis patients and 55 control healthy subjects. A complete eye examination and 6 mm × 6 mm OCTA imaging were performed. Retinal vascular status was evaluated by analyzing vascular density (VD) of superficial vascular plexus (superficial wVD) and deep vascular plexuses (deep wVD) in a 6 mm × 6 mm area and in foveal (superficial fVD and deep fVD) and parafoveal sectors (superficial pVD and deep pVD). In addition, foveal thickness (FT) and foveal avascular zone (FAZ) and clinical variables, including best corrected visual acuity (BCVA), intraocular pressure and refractive condition, were collected. RESULTS: BCVA, intraocular pressure and refractive condition were comparable between cases and controls. OCTA imaging showed that superficial wVD and superficial pVD were lower in the psoriasis group in comparison with controls (p = 0.009 and p = 0.01, respectively). Similarly, deep wVD and pVD were lower in the psoriasis group in comparison with control subjects (p = 0.03 and p = 0.01, respectively). In a sub-analysis of 47 patients affected by psoriasis without psoriatic arthritis, lower values of wVD and pVD in both superficial and deep capillary plexuses were registered. CONCLUSION: OCTA is a useful tool which provides data on vascular status of the retina in psoriasis with no ocular involvement. VD data may suggest that vascular changes may occur earlier than clinical onset of posterior inflammation.