Outer Retinopathies Associated with COVID-19 Infection: Case Reports and Review of Literature.

Background: The coronavirus disease (COVID-19) is a highly contagious disease with profound health implications. It can affect any part of the body with variable severity. Various ophthalmic manifestations of coronavirus disease have been documented. Case Presentations. We reported three cases of outer retinopathies associated with COVID-19 infection. All three patients were young females. The first two patients presented within days of COVID-19 infection with complaints of black spots in the eyes. Multimodal retinal imaging showed lesions consistent with acute macular neuroretinopathy. Lesions were bilateral in the first patient and unilateral in the second one. Our third patient presented with blurred vision in one eye, 3 months after a suspected COVID-19 infection. Retinal imaging showed outer retinopathy. Our patients' vision was good and maintained during the follow-up. All three were monitored on observation only, and symptoms and lesions improved with time. Conclusion: In conclusion, COVID-19-related thromboinflammatory response can result in localized vascular inflammation and hypoperfusion in any of the retinal capillary plexuses or choriocapillaris resulting in ischemia of the corresponding retinal or choroidal layers.

Real-World Experience in the Use of Immunosuppression for the Management of Inflammatory Eye Disease.

PURPOSE: Patients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal. METHODS: Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet's disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured. RESULTS: Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4-5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner. CONCLUSION: Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

Ocular Metastasis as First Presentation of Large-Cell Neuroendocrine Carcinoma.

Introduction: We report a rare case of an aggressive large-cell neuroendocrine lung tumour, which presented with ocular metastasis. Case Presentation: A 70-year-old lady presented with a 4-week history of left eye pain and photophobia. Ocular examination revealed left-sided episcleritis and she was treated with topical lubricants and steroids. However, she re-presented 6 months later with recurrent left eye symptoms and was found to have an iris stroma amelanotic lesion, posterior synechiae, 360-degrees rubeosis iridis, raised intraocular pressure, and trace vitreous inflammation. Ultrasound biomicroscopy revealed a left thickened iris with an associated ciliary body lesion. Sarcoid-related ocular inflammation was suspected, but a computed tomography (CT) scan of the lung revealed an incidental right upper lobe lesion. Histology from a transcorneal iris biopsy showed a high-grade neuroendocrine carcinoma, and the diagnosis of metastatic lung large-cell neuroendocrine carcinoma was confirmed via high-resolution CT scan, positron emission tomography scan, and CT-guided lung biopsy. She was given multiple courses of different chemotherapy regimens along with palliative radiotherapy. However, the tumour and its metastases continued to progress and she passed away 4 years after her initial presentation. Conclusion: Ocular metastatic large-cell neuroendocrine carcinoma is rare, and the first presentation with ocular metastasis is even rarer. This case highlights the importance of early detection of ocular metastases in order to hasten oncological treatment. A low threshold for systemic investigations and ophthalmology referral in cases of unexplained, refractory ocular symptomatology is essential, given the heterogeneous presentation, rarity, and poor prognosis of these tumours, even with maximal treatment.

Bilateral Panuveitis and Exudative Retinal Detachments Associated with Alpelisib.

We report a case of alpelisib-induced uveitis. A 68-year-old female who had recently been given alpelisib for metastatic breast cancer presented with a 2-week history of bilateral worsening vision with a corresponding acute hypermetropic shift. Her unaided visual acuity was 6/60 in both eyes, with bilateral anterior uveitis, non-granulomatous keratic precipitates, posterior synechiae, and limited fundal view. There was also a mild iris bombe configuration, although the intraocular pressures were normal. Ocular ultrasound revealed bilateral uveal effusion, ciliary body congestion, dense vitreous cells, and exudative retinal detachments. These findings were also confirmed on multimodal imaging with widefield fundus photography (Optos) and optical coherence tomography. Based on the clinical features above, a diagnosis of alpelisib-induced panuveitis was diagnosed. She was then admitted and treated with a 3-day course of intravenous methylprednisolone and intensive topical steroids. Her clinical signs and symptoms started to improve, and she was discharged 4 days later. At 1 week of follow-up, her best-corrected visual acuity was 6/12 in both eyes, with broken posterior synechiae and resolution of exudative retinal detachments. This case highlights the importance of early ophthalmology involvement by the oncology team as oncology therapy can have potential unexpected ocular manifestations.

Pathophysiological Aspects of Ocular Toxoplasmosis: Host-parasite Interactions.

PURPOSE: This review aims to present the state of the art to understand the pathophysiology of ocular toxoplasmosis (OT), providing further foundations that would help to improve the future treatment and prognosis of this potentially blinding disease. METHODS: A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items. RESULTS: Toxoplasma gondii ocular infection is one of the most frequent causes of posterior uveitis. Despite the ocular barriers, the parasite reaches the eye through different mechanisms. Once inside, it remains encysted livelong within the retina, and recurrences cannot be completely avoided. The complexity of host-parasite interactions, leading to the success of this parasite, encompasses host factors such as genetic predisposition, immune status, and age; and parasite factors such as strain diversity, virulence, phylogenetic origin, and geographical distribution. These factors influence the clinical presentation, course, and progression of the disease. Additional elements, such as pregnancy, eating behavior, and environmental, social, and cultural factors may also contribute to this complex balance. CONCLUSIONS: The host-parasite interaction in OT is a complex and multifactorial relationship, with the parasite always on the driving edge of the game. There are still multiple incompletely understood fields to be investigated. Future research would permit further insight into the immune-biology of the parasite and recognition of the host-parasite interplay to improve the diagnostic and management performance.

Ocular toxoplasmosis: a review of the current diagnostic and therapeutic approaches.

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up and therapeutic approach of ocular toxoplasmosis focusing mainly on the postnatally acquired form of the disease. METHODS: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. RESULTS: Ocular toxoplasmosis is one of the most frequent infectious etiologies of posterior uveitis. It typically presents with retinochoroiditis. Setting an accurate diagnosis depends to a considerable degree on detecting characteristic clinical characteristics. In addition to the evaluation of clinical features, the diagnosis of toxoplasmosis relies at a large degree on serologic testing. The detection of the parasite DNA in the aqueous or vitreous humor can provide evidence for a definitive diagnosis. The current mainstay for the treatment, if necessary, is the use of oral antibiotic with systemic corticosteroids. Recent evidence suggests other therapeutic approaches, such as intravitreal antibiotics can be used. CONCLUSION: Recent developments in the diagnostic and therapeutic approach have contributed to preventing or limiting vision loss of patients suffering from ocular toxoplasmosis. Further studies are required to provide a better understanding of epidemiology, pathogenesis, diagnosis, and treatment with a significant impact on the management of this challenging clinical entity.

Proposing a Neurotropic Etiology for Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Relentless Placoid Chorioretinitis.

Purpose: To reassess the underlying pathophysiology of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinitis (RPC) through comparison with the non-inoculated eye of the von Szily animal model of neurotropic viral retinal infection. Methods: Narrative review. Results: Literature reports of isolated neurotropic viral entities and rising serological viral titers in APMPPE after presentation support a potential direct infective etiology. In general, viral transport along axons results in mitochondrial stasis and disruption of axoplasmic flow. Clinical manifestations of axoplasmic flow disruption in APMPPE/RPC may signify the passage of virus along the neuronal pathway. From a case series of 11 patients, we demonstrate a timely, spatial, and proportional association of optic disc swelling with APMPPE lesion occurrence. Signs within the inner retina appear to precede outer retinal lesions; and acute areas of outer nuclear layer (ONL) hyperreflectivity appear to be the result of coalescence of multiple hyperreflective foci resembling axonal spheroids (which occur as a consequence of axoplasmic disruption) and follow the Henle fiber layer neurons. Underlying areas of retinal pigment epithelium (RPE) hyper-autofluorescence follow ONL hyperreflectivity and may signify localized infection. Areas of apparent choriocapillaris hypoperfusion mirror areas of RPE/Bruch's membrane separation and appear secondary to tractional forces above. Increases in choroidal thickness with lesion occurrence and focal areas of choriocapillaris hypoperfusion are observed in both APMPPE/RPC and the von Szily model. Conclusions: The neurotrophic infection model provides significant advantages over the existing primary choriocapillaris ischemia hypothesis to account for the range of imaging signs observed in APMPPE and RPC.

Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada disease is a rare, multisystem, autoimmune disorder with numerous clinical manifestations, mediated through a T-helper 1 response against melanocytes in the eye, inner ear, central nervous system, hair and skin. We describe a 20-year-old British-Honduran man with recent worsening headache and photophobia, vomiting and visual blurring. On examination, his pupils reacted sluggishly and visual acuities were bilaterally reduced. Optical coherence tomography showed gross retinal swelling and neurosensory detachments. MR scan of the brain was normal, but cerebrospinal fluid showed a reactive picture with 258 ×109 lymphocytes./L (normal ≤5×109/L). Following treatment with immunosuppression (prednisolone, tacrolimus, mycophenolate mofetil, adalimumab), he made a full recovery. Clinicians should consider Vogt-Koyanagi-Harada disease in patients presenting with headache with acute profound visual loss. A prompt diagnosis and immunosuppressive therapy can lead to complete resolution.

Quantitative analysis of vitreous inflammation using optical coherence tomography in patients receiving sub-Tenon's triamcinolone acetonide for uveitic cystoid macular oedema.

BACKGROUND/AIMS: To evaluate the vitreous signals obtained on spectral domain optical coherence tomography (SD-OCT) in patients with uveitic cystoid macular oedema (CMO) and compare these signals before and after sub-Tenon's triamcinolone acetonide injection. METHODS: Retrospective study with standardised longitudinal imaging preintervention and postintervention. The study cohort comprises 22 patients (22 eyes) with uveitic CMO receiving a sub-Tenon's triamcinolone acetonide (STTA) injection. Post hoc analysis of SD-OCT images using custom software provided an 'absolute' measurement of vitreous signal intensity, which was expressed as a ratio to the retinal pigment epithelium intensity ('VIT/RPE-relative intensity') in arbitrary units. MAIN OUTCOME MEASURE: Difference in VIT/RPE-relative intensity before and after treatment. RESULTS: Treatment with STTA resulted in a significant reduction in VIT/RPE-relative intensity, which was associated with both a reduction in central retinal thickness (CRT) and improvement in visual acuity. Mean (SD) VIT/RPE-relative intensity pretreatment was 0.139 (0.074) versus 0.053 (0.028) post-treatment (p=3×10-5). Mean (SD) CRT was 581 µm (119 µm) pretreatment versus 333 µm (95 µm) post-treatment (p=2×10-8); the mean reduction in CRT was 248 (95% CI 189 to 306). The correlation coefficient between VIT/RPE-relative intensity and CRT was 0.534 (p=0.011) and between VIT/RPE-relative intensity and visual acuity was 0.702 (p=0.0001). CONCLUSIONS: This study provides evidence that the OCT-derived VIT/RPE-relative intensity may be useful as a quantitative and objective marker of disease activity and treatment response in uveitis complicated by CMO. This first longitudinal study of this novel OCT parameter is an encouraging step in the development of sensitive objective OCT-based endpoints for trials of efficacy in uveitis.

Cortisol biosynthesis in the human ocular surface innate immune response.

Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) in OcS defense, remains unresolved. We found that primary human corneal epithelial cells (PHCEC), fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was independent of Toll-like receptor (TLR) activation. While PolyI∶C induced maximal cytokine and chemokine production from both PHCEC (IFNγ, CCL2, CCL3, and (CCL4), IL6, CXCL10, CCL5, TNFα) and PHKF (CCL2, IL-6, CXCL10, CCL5), only PHKF cytokines were inhibited by GCs. Both Poly I∶C and LPS challenged-corneal cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1 11ß-HSD1 activity (30 and 40% respectively). These data were supported by clinical studies demonstrating reduced human tear film cortisol∶cortisone ratios (a biomarker of local 11ß-HSD1 activity) in pseudomonas keratitis (1∶2.9) versus healthy controls (1∶1.3; p<0.05). This contrasted with putative TLR3-mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where an increase in cortisol∶cortisone ratio was observed (113.8∶1; p<0.05). In summary, cortisol biosynthesis in human corneal cells is independent of TLR activation and is likely to afford immunoprotection under physiological conditions. Contribution to ocular mucosal innate responses is dependent on the aetiology of immunological challenge.

Survey of expert practice and perceptions of the supporting clinical evidence for the management of uveitis-related cataract and cystoid macular oedema.

PURPOSE: To survey the practice of uveitis experts in the management of uveitic cataract and cystoid macular oedema (CMO). METHODS: A structured questionnaire containing two clinical scenarios was sent to members of the International Uveitis Study Group (IUSG). The questionnaire surveyed both respondents' current practice and their perception of the supporting clinical evidence. RESULTS: For uveitic cataract, 70% required a 3-month inflammation-free period before surgery, and 76% gave a prophylactic preoperative systemic corticosteroid. For uveitic CMO, 87% gave corticosteroids, usually orally. Preferred second-line agents were methotrexate (39%), cyclosporin (24%), azathioprine (17%), and mycophenolate (7%). Respondents suggested the evidence underlying their decisions was either absent or relatively weak (levels III or IV), and in most cases personal experience was a factor. CONCLUSIONS: This survey highlights areas of consensus and variation among uveitis experts in managing uveitic cataract and CMO, and emphasizes the need for further clinical trials to establish the best practice.

Bilateral ring scotomas following laser in situ keratomileusis.

A 53-year-old white man who had a history of transient ocular hypertension had bilateral laser in situ keratomileusis (LASIK) for myopia. Subsequent computerized static perimetry revealed bilateral, persistent, repeatable midperipheral ring scotomas. The pre-LASIK visual fields were within normal limits, and the optic discs appeared stable and not diagnostic for glaucomatous optic neuropathy. A comprehensive baseline data set before laser refractive surgery aids subsequent assessment of individuals at high risk for developing glaucoma.