A retrospective study describing the effective exchange of total blood plasma for disease control in the exacerbation of serpiginous choroiditis.

INTRODUCTION: Serpiginous choroiditis presents with large yellow-white exudative lesions that occur near the optic nerve papillae, that progresses slowly with repeated relapses and cures. Although infection and autoimmunity have been implicated, the cause is unknown. METHODS: A man was diagnosed with serpiginous choroiditis on clinical and other examinations. He started treatment with oral corticosteroids, cyclophosphamide, adalimumab, azathioprine, rituximab, and mycophenolate mofetil. Only the steroids and cyclophosphamide had a therapeutic effect. Plasma exchange was initiated, and the lesions quickly resolved. RESULTS: Disease control has been maintained by plasma exchange and cyclophosphamide during flare-ups in the fall and winter, suggesting that plasma exchange is effective in the treatment of serpiginous choroiditis. CONCLUSION: The reproducible response with each recurrence suggests a strong association between the disease and autoimmunity. Furthermore, that some, as yet unknown, autoantibodies are involved in the pathogenesis of serpiginous choroiditis.

Surgical Treatment for a Full-Thickness Macular Hole That Developed on a Large Drusenoid Pigment Epithelial Detachment.

Full-thickness macular hole (FTMH) and age-related macular degeneration (AMD) can affect the same eyes in the older population. Previously reported phenotypes of AMD concurrent with FTMH include early/intermediate AMD and serous pigment epithelial detachment (PED). A 68-year-old woman presented to our clinic with decreased vision due to a cataract and a large drusenoid PED in both eyes. After ruling out choroidal neovascularization, she underwent cataract surgery. Three days after the cataract surgery, an FTMH was found in the left eye. Although the FTMH was not closed after the initial pars plana vitrectomy (PPV) with the inner limiting membrane (ILM) peeling and air tamponade, it was closed after reoperation with additional ILM peeling, retinal massage, and SF6 gas tamponade. Best-corrected visual acuity (BCVA) was improved from 20/60 before the first PPV to 20/40 at six months after the reoperation. Some large soft drusen in the macula were fused after surgeries in the operated eye, but not in the fellow eye. An FTMH concurrent with a large drusenoid PED is rare. It can be closed surgically, and postoperative visual function can improve.

Fovea-Sparing as Opposed to Total Peeling of Internal Limiting Membrane for Myopic Foveoschisis: A Systematic Review and Meta-analysis.

TOPIC: The effectiveness of fovea-sparing (FS) peeling of internal limiting membrane (ILM) to treat myopic foveoschisis (MF) has not been understood fully. The present meta-analysis aimed to compare postoperative visual and anatomic outcomes between FS peeling and total peeling (TP) of ILM in pars plana vitrectomy for the treatment of MF. CLINICAL RELEVANCE: Postoperative macular hole (MH) development is not uncommon and is a serious complication after surgery for MF, with poor visual prognosis. Fovea-sparing peeling of ILM is expected to reduce the risk of postoperative MH; however, no statistically significant evidence exists to prove this hypothesis. In addition, its effect on postoperative visual acuity has not been clear. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were reviewed systematically, and studies that compared FS with total ILM peeling in MF surgery were retrieved. The protocol was registered in International Prospective Register of Systematic Reviews (identifier, CRD42020201675). Primary outcome measures were the postoperative best-corrected visual acuity (BCVA) and frequency of postoperative MH development. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Eight studies with 300 eyes from 289 patients were included. All studies were nonrandomized and observational. The postoperative BCVA was significantly better in eyes treated with FS (mean difference [MD], -0.15 logarithm of the minimum angle of resolution [logMAR]; 95% confidence interval [CI], -0.24 to -0.05 logMAR; P = 0.002). The risk of postoperative MH was significantly lower in the FS group (odds ratio, 0.19; 95% CI, 0.06-0.56; P = 0.003). No significant difference was found in postoperative central foveal thickness (MD, 12.59 µm; 95% CI, -2.8 to 28.0 µm; P = 0.11). The certainty of evidence regarding lower frequency of postoperative MH after FS peeling was considered moderate, whereas the certainty regarding better postoperative BCVA after FS peeling was judged to be low. DISCUSSION: Fovea-sparing peeling may contribute to better visual acuity outcome and lower risk of postoperative MH development in eyes with MF.

Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy.

OBJECTIVE: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged ≥ 2 months in the United States, and is currently under Health Authority review in the EU. METHODS: Subjects included patients with SMA aged 2 months-60 years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age-appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2-6 months depending on study and assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study. RESULTS: A total of 245 patients receiving risdiplam were assessed. Comprehensive, high-quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD-OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam-induced toxicity and resolved with ongoing treatment. INTERPRETATION: Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.

Pathologic myopia: an overview of the current understanding and interventions.

Pathologic myopia is a major cause of low vision and blindness worldwide. Its social and economic burden has been demonstrated by epidemiological studies. There have been recent advances in the classification system for myopic maculopathy that enables clinicians to describe different types of lesions, including tessellated fundus, diffuse/patchy chorioretinal atrophy, macular atrophy, lacquer cracks, choroidal neovascularization (CNV), and Fuchs' spot, in a standardized format. From a therapeutic point of view, anti-vascular endothelial growth factor therapy has been established as first-line choice for myopic CNV. For myopic retinoschisis and macular holes with/without retinal detachment, pars plana vitrectomy has been generally accepted as an efficient strategy. Studies are being conducted to determine how to avoid the development of a postoperative macular hole and to improve the quality of vision after surgery. In recent years, studies have revealed preventive measures that can be taken against myopia progression, including low-dose atropine eyedrops and contact lens wearing with peripheral myopic defocusing.

Using flowchart for ophthalmic consultations in hospitalized patients with COVID-19.

Ocular complications of coronavirus disease 2019 (COVID-19) do not essentially cause serious visual loss. However, due to the characteristics of this disease, delays in diagnosis and treatment in hospitalized patients may leave them with serious visual impairment. If conjunctivitis is suspected, ophthalmological follow-up is needless because it is expected spontaneous healing. Diplopia is often complicated for extra-ocular neurological findings and need neurological consults. Ophthalmologists should be consulted for ocular surface disease, high intraocular pressure, and ocular inflammation that may cause visual loss if patients complain of blurred vision, visual loss, and ocular pain. The problem is unconscious patients with risk of developing high intraocular pressure or keratitis. An ophthalmologist should be consulted as soon as possible if eye redness or pupil abnormalities appear in these patients. We developed a flowchart for ophthalmic consultations in hospitalized patients with COVID-19, for facilities where an ophthalmologist is not always present, and for third or fourth waves or, a pandemic of another infectious disease.

Spectral domain optical coherence tomography and fundus autofluorescence findings in cytomegalovirus retinitis in HIV-infected patients.

PURPOSE: To assess the usefulness of spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) findings in cytomegalovirus (CMV) retinitis. STUDY DESIGN: Observational case series. METHODS: Thirteen eyes of 11 human immunodeficiency virus (HIV)-positive patients with CMV retinitis underwent full ophthalmologic examinations, SD-OCT, and 4 eyes of 4 patients underwent FAF. FAF images included short-wavelength autofluorescence (SW-AF) and near-infrared autofluorescence (IR-AF). CMV retinitis was classified into proposed categories of acute, subacute, remission, and recurrent; the acute stage was further subdivided into initial, early, and late stages. RESULTS: In the initial stage, vertical structural disruption of all retinal layers was observed by SD-OCT, and FAF showed hyperautofluorescence on SW-AF and hypoautofluorescence on IR-AF. In the early stage, SD-OCT showed significant retinal thickening; cells and debris from the retinal surface to the vitreous; enlarged vessels with/without thickened vessel walls; and highly complicated serous retinal detachment. In the late to subacute stage, features observed included rhegmatogenous retinal detachment with shrinking posterior hyaloid membrane and waving from the ellipsoid zone to the retinal pigment epithelium. In remission, FAF findings were hypoautofluorescence on SW-AF and hyperautofluorescence on IR-AF. CONCLUSION: Although the number of examined eyes was limited, SD-OCT and FAF provide new information in various stages of CMV retinitis in patients with HIV infection that is not obtainable by conventional examination and which may be of great benefit when screening for the initial stage of CMV retinitis.

Time to development of ocular syphilis after syphilis infection.

To provide an estimate of the incubation period of ocular syphilis based on serology using both clinical data and stored serum samples, we retrospectively reviewed patients with HIV-1 infection who presented with ocular syphilis between August 1997 and July 2015 in a tertiary hospital in Japan. The incubation period of ocular syphilis was defined as the time from syphilis infection to the development of ocular symptoms due to ocular syphilis. During the study period, 20 patients were diagnosed with ocular syphilis and 8 patients were enrolled in the present study. All patients were Japanese men who have sex with men with a median age of 46 years (IQR 41.5-53.5). The median CD4 count was 668.5/µL (IQR 567.8-734.3) and 5 of the 8 patients had HIV-1 viral load of less than 50 copies/mL. All study patients presented to our clinic because of the development of ocular symptoms, and they did not have any other symptoms compatible with primary, secondary, or tertiary syphilis. The median time between syphilis infection and development of ocular symptoms was 11 months (IQR 4-19, range 2.5-45). Seven out of eight (87.5%) cases developed ocular syphilis within 2 years of syphilis infection. Ocular syphilis should be suspected even in patients with early syphilis who present with ocular symptoms. Moreover, routine serologic screening for syphilis among patients with HIV-1 infection is critical for prevention of irreversible visual loss in ocular syphilis cases.

Prognosis of ocular syphilis in patients infected with HIV in the antiretroviral therapy era.

OBJECTIVE: To describe the clinical course and prognosis of ocular syphilis in patients infected with HIV-1 in the antiretroviral therapy (ART) era. METHODS: We conducted a single-centre retrospective chart review of ocular syphilis in patients infected with HIV-1 diagnosed between August 1997 and July 2015. The prognosis of best-corrected visual acuity (BCVA) was analysed. RESULTS: The study subjects were 30 eyes of 20 men who had sex with men (MSM) (median age, 41). Loss of vision and posterior uveitis were the most common ocular clinical features (43%) and location of inflammation at presentation (50%), respectively. The median baseline BCVA was 0.4 (IQR 0.2-1.2), including three eyes with hand motion. BCVA≤0.4 at diagnosis was significantly associated with posterior uveitis or panuveitis (p=0.044). Seventy-five per cent were treated with intravenous benzylpenicillin and 53% were diagnosed with neurosyphilis. After treatment (median follow-up: 21 months), BCVA improved in 89% of the eyes, including all eyes with hand motion, to a median BCVA of 1.2 (IQR 0.8-1.2). Kaplan-Meier analysis showed that >28 days of ocular symptoms before diagnosis was the only factor associated with poor prognosis of BCVA. Three patients (15%) developed recurrence after treatment. CONCLUSIONS: The prognosis of BCVA in HIV-infected patients with ocular syphilis in the ART era was favourable after proper treatment. Having >28 days of ocular symptoms before diagnosis was associated with poor prognosis. Changes in visual acuity in HIV-infected MSM should prompt an immediate assessment for ocular syphilis as delays in diagnosis and therapy can lead to irreversible visual loss.

Routine Eye Screening by an Ophthalmologist Is Clinically Useful for HIV-1-Infected Patients with CD4 Count Less than 200 /µL.

OBJECTIVE: To investigate whether routine eye screening by an ophthalmologist in patients with HIV-1 infection is clinically useful. METHODS: A single-center, retrospective study in Tokyo, Japan. HIV-1-infected patients aged over 17 years who visited our clinic for the first time between January 2004 and December 2013 and underwent full ophthalmologic examination were enrolled. At our clinic, ophthalmologic examination, including dilated retinal examination by indirect ophthalmoscopy was routinely conducted by ophthalmologists on the first visit. The prevalence of ophthalmologic diseases and associated factors including the existence of ocular symptoms were analyzed. RESULTS: Of the 1,515 study patients, cytomegalovirus retinitis (CMV-R) was diagnosed in 24 (2%) patients, HIV retinopathy (HIV-R) in 127 (8%), cataract in 31 (2%), ocular syphilis in 4 (0.3%), and uveitis with unknown cause in 8 (0.5%). Other ocular diseases were diagnosed in 14 patients. The CD4 count was <200 /µL in all CMV-R cases and 87% of HIV-R. The prevalence of any ocular diseases, CMV-R, and HIV-R in patients with CD4 <200 /µL were 22%, 3%, and 15%, respectively, whereas for those with CD4 ≥200 /µL were 5%, 0%, and 2%, respectively. No ocular symptoms were reported by 71% of CMV-R cases and 82% of patients with any ocular diseases. CONCLUSIONS: Routine ophthalmologic screening is recommended for HIV-1-infected patients with CD4 <200 /µL in resource-rich settings based on the high prevalence of ocular diseases within this CD4 count category and because most patients with ocular diseases, including those with CMV-R, were free of ocular symptoms.

[Multimodal imaging of a case of acute syphilitic posterior placoid chorioretinitis].

BACKGROUND: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare manifestation of ocular syphilis. We report on multimodal imaging including ophthalmoscopy, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA) and indocyanine green angiography (IA) of a case diagnosed with ASPPC. CASE: A 45-year-old man who was positive for human immunodeficiency virus presented with a 2-week history of visual loss in the right eye. CLINICAL FINDINGS: Ophthalmoscopy showed a unilateral yellowish lesion involving the macula. SD-OCT revealed absence of the photoreceptor inner segment ellipsoid as well as an absent external limiting membrane, and nodular elevations of the retinal pigment epithelium layer at the macula. Late IA demonstrated punctate hypofluorescent dots in diffuse hyperfluorescent area corresponding to the macular lesion. Serologic tests were positive for syphilis and the patient was treated with intravenous penicillin G. Visual acuity improved with treatment from 20/100 to 20/16 and the retinal appearance returned to normal. There was completely restored stratification of the outer retina after therapy. CONCLUSION: In the present case of ASPPC, the SD-OCT imaging demonstrated characteristic abnormalities including RPE nodularity which showed hypofluorescent dots on late IA.

Diagnostic utility of quantitative plasma cytomegalovirus DNA PCR for cytomegalovirus end-organ diseases in patients with HIV-1 infection.

OBJECTIVE: To investigate the diagnostic value of quantitative plasma cytomegalovirus (CMV)-DNA polymerase chain reaction (PCR) for CMV end-organ diseases (CMV-EOD) in patients with HIV-1 infection. DESIGN: Single-center cross-sectional study. METHODS: The study subjects were HIV-1-infected patients with CD4 ≤200 per microliter, who had undergone ophthalmologic examination with plasma CMV-DNA PCR measured within 7 days. CMV retinitis and other CMV-EOD were diagnosed according to the ACTG criteria. PCR value was converted into the WHO international standard. RESULTS: CMV retinitis and all CMV-EOD were diagnosed in 23 (5%) and 37 (8%) of the 461 study patients, respectively. CMV-DNA was undetectable (<185 IU/mL) in 2 patients with CMV retinitis and 1 with encephalitis. The area under the receiver operating characteristic curve of CMV-DNA for CMV retinitis and all CMV-EOD were 0.80 [95% confidence interval (CI): 0.71 to 0.89] and 0.82 (0.75 to 0.89), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for each cutoff value of CMV-DNA were as follows: for CMV retinitis, ≥10,086 IU/mL: 26.1%, 94.1%, 18.8%, 96%; ≥2946 IU/mL; 56.5%, 86.8%, 18.3%, 97.4%; ≥959 IU/mL; 60.9%, 78.1%, 12.7%, 97.4%; detectable CMV-DNA (≥185 IU/mL): 91.3%, 48.2%, 8.5%, 99.1%; for all CMV-EOD: ≥10,086 IU/mL: 32.4%, 95.3%, 37.5%, 94.2%; ≥2946 IU/mL; 54.1%, 88%, 28.2%, 95.6%; ≥959 IU/mL; 62.2%, 79.5%, 20.9%, 96%; detectable CMV-DNA; 91.9%, 49.5%, 13.7%, 98.6%. CONCLUSIONS: Plasma CMV-DNA PCR has a high diagnostic value for both CMV retinitis and all CMV-EOD in patients with advanced HIV-1 infection. A cutoff value of CMV-DNA ≥10,086 IU/mL and ≥2946 IU/mL yields high specificity, whereas undetectable CMV-DNA load (<185 IU/mL) likely rules out CMV-EOD.

Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia.

Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/µl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/µl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.

Brainstem Infarction and Panuveitis due to Sarcoidosis Successfully Treated with Steroid Pulse Therapy.

A 36-year-old man visited our hospital because of blurred vision and redness of the conjunctiva. Slit-lamp examination showed panuveitis. Two days later, he suddenly experienced dizziness, speech disturbance, paralysis of his right extremities, and gait disturbances. Neurological examinations suggested that his symptoms were caused by a left lateral medullary lesion. He also had erythema mainly on his trunk. Magnetic resonance imaging (MRI) of his brain demonstrated a small infarct on the left side of the medulla oblongata. Clinical presentation and MRI findings were consistent with the diagnosis of a Wallenberg's syndrome. He also had bilateral hilar lymphadenopathy. A skin biopsy showed granulomatous nodular dermatitis compatible with sarcoidosis. He was treated with steroid pulse therapy and his neurological and ocular symptoms immediately improved. Only seven similar cases of intracranical sarcoidosis have been reported, but none had been treated with steroid pulse therapy. We recommend that steroid pulse therapy be considered to treat patients with sarcoidosis with signs of lesions in the central nervous system.

[Severe case of cytomegalovirus-associated immune reconstitution syndrome in AIDS].

BACKGROUND: Immune reconstitution syndrome (IRS) is a complication caused by reactivation of the immune system that can occur after starting highly active antiretroviral therapy (HAART) in patients with acquired immunodeficiency syndrome (AIDS). Severe IRS associated with cytomegalovirus (CMV) in both eyes who had lost his left vision is reported. CASE: A 37-year-old man with AIDS who had started HAART discontinued his medication. Two weeks after the re-induction of HAART, he suffered CMV retinitis OU. Vitreous opacity OU appeared 3 days later, and optic neuritis OS appeared 6 days after the onset; and visual acuity OS decreased to 0.06. As the number of CD 4 positive T lymphocytes (CD 4) increased from 39 to 118/microl in both the pre- and- post HAART, we diagnosed IRS and started anti- CMV and systemic steroid therapy and discontinued the HAART. The focus of CMV retinitis was improved; however, visual acuity OS did not improve. CONCLUSION: Severe IRS with visual loss induced by CMV retinitis after HAART needs to be considered in low CD 4 level patients during the induction phase.

[Ocular complications in patients with human immunodeficiency virus infection].

PURPOSE: To evaluate the recent clinical manifestations of ocular complications in patients with human immunodeficiency virus(HIV) infection. METHODS: We retrospectively reviewed the medical records of 94 new HIV-positive patients examined at the International Medical Center of Japan between April 1, 2002, and March 31, 2003, and listed the details of ocular complications. The use of highly active antiretroviral therapy (HAART) and CD 4 cell counts was also recorded in patients with cytomegalovirus (CMV) retinitis and iritis/vitritis. RESULTS: The following ocular complications were recognized in 31 patients: retinal microvasculopathy (11 cases), CMV retinitis (10 cases), inactive inflammatory changes (6 cases), iritis/vitritis (5 cases), optic nerve atrophy (2 cases), papilledema (2 cases), ocular tuberculosis (1 case), progressive outer retinal necrosis (1 case) and conjunctival Kaposi's sarcoma (1 case). In patients with CMV retinitis, the CD 4 cell counts at the onset were lower than 50/microl except in 1 case. Iritis and/or vitritis were recognized in 5 cases, and the onset of 4 cases occurred after the beginning of HAART. Among the patients studied, immune recovery uveitis was suspected in 3 patients with a history of CMV retinitis. CONCLUSIONS: Ocular complications were recognized in almost one third of the patients in our series. Immune recovery uveitis was suspected in 3 patients with iritis/vitritis who previously had CMV retinitis.