Bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus infection: a case report.

BACKGROUND: To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement. CASE PRESENTATION: A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates. CONCLUSIONS: In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.

Ophthalmic manifestations as the first presenting feature in dengue fever: a 10-year study.

Purpose: To report patients who first presented with various ocular manifestations and eventually ascertained to have underlying dengue. Methods: A prospective study was conducted at multiple tertiary eye-care centers in India from 2012 to 2022. Cases reporting initially with ocular features along with fever/past history of fever over the last two weeks or with clinical features of dengue were selected. After an ophthalmological examination, patients underwent complete serological and biochemical analysis and those with reduced platelet counts were evaluated for dengue. Results: Out of 564 cases, 15 patients were verified to be afflicted with dengue eventually. A rising trend of cases was seen every year and out of 15 cases, eight cases were reported during the Covid-19 pandemic (from 2020 to 2022), but were COVID-negative. 9 cases presented with acute redness followed by diminished vision. Seven cases presented a history of fever over the last few days and one had traveled from dengue endemic area. The various ocular presentations included subconjunctival hemorrhage, viral keratitis, anterior uveitis, sixth-nerve palsy, and vitreous hemorrhage. On serological examination, all 15 patients were detected to have low platelets. All cases responded well with supportive treatment and the ocular features subsided in all within a couple of weeks with good visual recovery. Conclusion: In a tropical nation, such as India, with endemic dengue zones and increasing figures of dengue lately, ophthalmologists must include dengue fever among the differential diagnoses in various ocular presentations like subconjunctival hemorrhage, viral keratitis, anterior uveitis, sixth nerve palsy, and vitreous hemorrhage. Abbreviations: DHF = dengue hemorrhagic fever, PCR = polymerase chain reaction, RT-PCR = real-time automated reverse transcriptase (RT-PCR), SD = standard deviation, MAC-ELIS = IgM antibodies capture enzyme-linked immunosorbent assay, RE = right eye, LE = left eye, CECT = Contrast-enhanced computed tomography.

Multitask Deep Learning for Joint Detection of Necrotizing Viral and Noninfectious Retinitis From Common Blood and Serology Test Data.

Purpose: Necrotizing viral retinitis is a serious eye infection that requires immediate treatment to prevent permanent vision loss. Uncertain clinical suspicion can result in delayed diagnosis, inappropriate administration of corticosteroids, or repeated intraocular sampling. To quickly and accurately distinguish between viral and noninfectious retinitis, we aimed to develop deep learning (DL) models solely using noninvasive blood test data. Methods: This cross-sectional study trained DL models using common blood and serology test data from 3080 patients (noninfectious uveitis of the posterior segment [NIU-PS] = 2858, acute retinal necrosis [ARN] = 66, cytomegalovirus [CMV], retinitis = 156). Following the development of separate base DL models for ARN and CMV retinitis, multitask learning (MTL) was employed to enable simultaneous discrimination. Advanced MTL models incorporating adversarial training were used to enhance DL feature extraction from the small, imbalanced data. We evaluated model performance, disease-specific important features, and the causal relationship between DL features and detection results. Results: The presented models all achieved excellent detection performances, with the adversarial MTL model achieving the highest receiver operating characteristic curves (0.932 for ARN and 0.982 for CMV retinitis). Significant features for ARN detection included varicella-zoster virus (VZV) immunoglobulin M (IgM), herpes simplex virus immunoglobulin G, and neutrophil count, while for CMV retinitis, they encompassed VZV IgM, CMV IgM, and lymphocyte count. The adversarial MTL model exhibited substantial changes in detection outcomes when the key features were contaminated, indicating stronger causality between DL features and detection results. Conclusions: The adversarial MTL model, using blood test data, may serve as a reliable adjunct for the expedited diagnosis of ARN, CMV retinitis, and NIU-PS simultaneously in real clinical settings.

Krupple-like factor 4 (KLF4) methylation signature in host cell in active viral keratitis with epithelial manifestation.

HSV1 presents as epithelial or stromal keratitis or keratouveitis and can lead to sight-threatening complications. KLF4, a critical transcription factor, and regulator of cell growth and differentiation, is essential in corneal epithelium stratification and homeostasis. Here, we want to understand the epigenetic modification specifically the methylation status of KLF4 in epithelium samples of HSV1 keratitis patients. After obtaining consent, epithelial scrapes were collected from 7 patients with clinically diagnosed HSV1 keratitis and 7 control samples (patients undergoing photorefractive keratectomy). Genomic DNA was isolated from the collected samples using the Qiagen DNeasy Kit. Subsequently, bisulfite modification was performed. The bisulphite-modified DNA was then subjected to PCR amplification using specific primers designed to target the KLF4, ACTB gene region, allowing for the amplification of methylated and unmethylated DNA sequences. The amplified DNA products were separated and visualized on a 3% agarose gel. KLF4 hypermethylation was found in 6 out of 7 (85.71%) eyes with viral keratitis, while 1 eye showed hypomethylation compared to PRK samples. Out of these 6, there were 2 each of epithelial dendritic keratitis, epithelial geographical keratitis, and neurotrophic keratitis. The patient with hypomethylated KLF4 had a recurrent case of HSV1 keratitis with multiple dendrites and associated vesicular lesions of the lip along with a history of fever. KLF4 hypermethylation in most viral keratitis cases indicated the under functioning of KLF4 and could indicate a potential association between KLF4 hypermethylation and the development or progression of HSV1 keratitis.

OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

Fundus imaging features of congenital rubella retinopathy.

PURPOSE: To evaluate the clinical characteristics of congenital rubella retinopathy (CRR) with modern fundus imaging. METHODS: Single-center case series. Eleven patients (2005-2020) at the Emory Eye Center with known or presumed CRR. Trained image readers reviewed fundus imaging (color fundus photography, widefield pseudocolor imaging, near-infrared reflectance imaging, autofluorescence imaging, and spectral-domain optical coherence tomography) for pre-specified features suggestive of CRR. RESULTS: Eleven patients with confirmed (63.6%) or presumed (36.3%) CRR were identified. All were female with median (range) age of 53 (35-67) years. Six (54.5%) were born during the 1964-1965 United States rubella epidemic. All had congenital hearing loss. Two (18.2%) had a congenital heart defect. Eleven (50.0%) eyes had salt-and-pepper retinal pigmentary changes. Twenty-two eyes (100.0%) had irregularly distributed regions of speckled hypoautofluorescence. One eye (4.5%) had a presumed macular neovascularization. CONCLUSION: Modern fundus imaging demonstrates characteristic features of CRR, even when pigmentary changes are not readily apparent on examination. Widefield autofluorescence findings of irregularly distributed speckled hypoautofluorescence are particularly revealing. This series of newly diagnosed adults with CRR may represent the milder end of the phenotypic spectrum of this condition, highlighting imaging findings that may aid in diagnostically challenging cases of CRR.

Clinical features of 26 cases of COVID-19-associated conjunctivitis.

PURPOSE: To explore the clinical features of COVID-19-associated conjunctivitis with the objective of preventing the spread of infection. STUDY DESIGN: Retrospective cohort study. METHODS: From March 2020 to March 2021, we retrospectively reviewed 26 (9.8%) consecutive COVID-19 patients with conjunctivitis among 282 COVID-19 cases admitted to our hospital. Clinical symptoms, onset date of conjunctivitis, time to patient recovery, and eye drop intervention were investigated. In addition, risk factors for developing conjunctivitis were statistically examined among 206 inpatients available for within 5 days of the onset. A multivariate analysis of conjunctivitis risk factors was performed. RESULTS: Among the 282 COVID-19 patients, 4 (1.4%) had conjunctival hyperemia as the primary symptom. The median time of onset was 4 days after the COVID-19 onset. Hyperemia was observed in all cases, but other ocular symptoms were rare. The median duration of hyperemia was 3 days. A multiple logistic regression analysis revealed that a young age (p=0.005) and current smoking habit (p=0.027) were independent risk factors for conjunctivitis after COVID-19. CONCLUSIONS: COVID-19-associated conjunctivitis is rare in the elderly and strongly associated with a history of smoking. It often occurs in the early stages of infection, and while hyperemia is recognized as a clinical symptom, other ocular symptoms are rare or non-existent. Many cases recover within a short time.

Antiviral treatment for acute retinal necrosis: A systematic review and meta-analysis.

Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).

Viral infections and pathogenesis of glaucoma: a comprehensive review.

SUMMARYGlaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.

Rubella virus-associated uveitis at a tertiary care hospital in Germany between 2013 and 2019.

Uveitis is a process of intraocular inflammation that may involve different sections of the uveal tract. Apart from systemic or localized immune-mediated diseases, infections are key players in the etiology of uveitis and entail different treatment strategies. Rubella virus (RuV) is a recognized causative agent for the development of Fuchs uveitis, representing a major cause of virus-associated intraocular inflammation. A cohort of 159 patients diagnosed with different forms of uveitis between 2013 and 2019 was subjected to diagnostic antibody testing of the aqueous or vitreous humor. The diagnostic panel included RuV, cytomegalovirus, herpes simplex virus, varicella-zoster virus, and toxoplasmosis. Within this cohort, 38 RuV-associated uveitis (RAU) patients were identified based on a pathologic Goldman-Witmer coefficient indicative of an underlying RuV infection. With a mean age of 45.9 years, the RAU patients were younger than the non-RAU patients (56.3, p < 0.001). The evaluation of clinical parameters revealed a predominance of anterior uveitis and late sequalae such as cataract and glaucoma among the RAU patients. In 15 of the patients a history of prior RuV infections could be confirmed. The study underlines the importance of long-term surveillance of RuV associated diseases that originate from infections before the introduction of RuV vaccination programs.

Iris depigmentation and cytomegalovirus in aqueous humor as predictors of uveitic activity and recurrence in chronic and recurrent anterior uveitis.

PURPOSE: To examine the clinical outcomes in chronic or recurrent anterior uveitis in the presence or absence of cytomegalovirus (CMV) and investigate the predictive factors for uveitic activity and recurrence. METHODS: Polymerase chain reaction (PCR) was performed in a prospective cohort of immunocompetent adults with recurrent or chronic anterior uveitis to detect CMV in aqueous humor. The clinical outcomes were compared between eyes with and without CMV DNA. Logistic regression was performed to evaluate associations between iris depigmentation, CMV-PCR status, uveitic activity, and recurrence. RESULTS: Thirty-eight eyes of 38 subjects with a mean age of 61.1 ± 11.2 years old were analyzed. Fifteen eyes were positive for CMV. More eyes with CMV developed recurrences and remained actively inflamed at 6, 12, and 24 weeks though the differences were insignificant. The presence of iris depigmentation was predictive of a greater odd of uveitic recurrences by 12 and 24 weeks (Odds ratio (OR) = 9.17 and 5.72, P = 0.007 and 0.034 respectively), whereas positive CMV-PCR predicts a greater odd of uveitic activity at postoperative 12 and 24 weeks (OR = 13.08, 34.30; P = 0.027, 0.007). CONCLUSION: Eye with and without detectable CMV behaved similarly in their clinical course. Our findings suggested that iris depigmentation was predictive of more frequent uveitic recurrence, regardless of the PCR status, whereas the presence of CMV in aqueous humor was associated with persistent uveitic activity. Iris changes may be present during the earlier phase of the disease and precede the detection of virus from the aqueous humor at a later stage of CMV infection.

PRIMARY CENTRAL NERVOUS SYSTEM AND VITREORETINAL LYMPHOMA MIMICKING VIRAL RETINITIS IN A YOUNG PATIENT.

BACKGROUND/PURPOSE: The purpose of this study was to report a young immunocompetent patient with primary central nervous system and vitreoretinal lymphoma initially presenting with peripheral retinitis. METHODS: This study is a case report. RESULTS: A 31-year-old woman presented with 20/60 vision in her left eye, vitreous haze, and peripheral retinal whitening. Intravitreal and oral antivirals were initiated for presumed acute retinal necrosis. Anterior chamber paracentesis was negative for viral nucleotide. Subretinal infiltrates developed, and vitreous biopsy was performed and interpreted as "negative except for rare yeast." Antifungal therapy was initiated. She developed multiple unilateral cranial neuropathies with multifocal areas of enhancement on neuroimaging. Lumbar puncture cytology was negative for neoplastic cells. After further worsening, aforementioned specimens were sent to a specialized ophthalmic pathology laboratory and the diagnosis revised to lymphoma of the diffuse B-cell type. Initial disease regression was seen after combined systemic and intraocular chemotherapy; unfortunately, the patient suffered a central nervous system recurrence and died from systemic complications 1 year later. CONCLUSION: There has been an increased incidence of primary central nervous system and vitreoretinal lymphoma in young patients. Although vitreous biopsy is the diagnostic gold standard for vitreoretinal lymphoma, a risk of false negative interpretation exists. A high index of suspicion and expert interpretation of pathology may be necessary to secure the correct diagnosis.

Spontaneous Regression of Choroidal Neovascularization in a Girl with Rubella Retinopathy.

Rubella retinopathy is usually a benign disorder with low impact on visual acuity. However, choroidal neovascularization can occur in these patients threatening their vision. We report the case of a 6-year-old girl with rubella retinopathy who developed a neovascular membrane and was successfully managed with observation. Decision to treat or observe in these patients must be carefully weighed, with both options being valid depending mainly on the location of the neovascular complex.

Cytomegalovirus Uveitis: Taiwan expert consensus.

Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations and treatment modalities. Based on expert consensus in Taiwan, this article provides suggestions regarding clinical manifestations, diagnosis, and treatment strategies for CMV uveitis based on clinical practice experience in Taiwan. CMV uveitis may have a distinct clinical presentation. Polymerase chain reaction (PCR) is an essential diagnostic tool to confirm a diagnosis. Antiviral therapy is the mainstay of treatment. Different agents, routes, and other supplemental treatments have been summarized and discussed in this article. Early diagnosis and appropriate treatment of CMV uveitis are crucial to avoid irreversible complications and vision loss. This consensus provides practical guidelines for ophthalmologists in Taiwan.

First-line management of necrotizing herpetic retinitis by prioritizing the investigation of immune status and prognostic factors for poor visual outcomes.

PURPOSE: To review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR. METHODS: Retrospective evaluation of a series of patients with NHR at our tertiary center between 2012 and 2021 using demographic, clinical, ophthalmologic, virological, therapeutic, and prognostic characteristics was performed. Patients were classified by NHR type: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis. RESULTS: Forty-one patients with NHR were included: 59% with ARN, 7% with PORN, and 34% with CMV retinitis. All patients with CMV retinitis and PORN were immunocompromised versus 21% of patients with ARN. CMV infection was found in 14 (34%) patients, varicella zoster virus infection in 14 (34%) patients, herpes simplex virus type 2 infection in 8 (20%) and type 1 infection in 5 (12%) patients. Intravenous antiviral therapy was received by 98% of patients and intravitreal antiviral injections by 90% of patients. The overall complication rate during follow-up was 83% of eyes. Most frequent complications were retinal detachment (33% eyes) and retinal break (29% eyes). Prognostic factors for poor visual outcomes were pre-existing monocular vision loss in contralateral eye among 17% of patients, bilateral NHR in 17% of patients, posterior pole involvement in 46% of eyes, and involvement > 2 retinal quadrants in 46% of eyes. CONCLUSIONS: The visual prognosis of patients with NHR remains poor. Prompt investigation of immune status and presence of factors justifying intravitreal antiviral injections must be prioritized to initiate and adapt management while awaiting causative virus confirmation.

A study on childhood microbial keratitis in South India.

Purpose: The aim of this study was to determine the predisposing risk factors, clinical characteristics, microbiological profile, and visual and functional treatment outcome of microbial keratitis including viral keratitis in children. Methods: A prospective study was carried out in a tertiary care institute over a period of 18 months on 73 pediatric patients. Data collected was analyzed for demographics of the patient population, causative organisms, and management outcome in terms of visual and functional outcome. Results: Patients in the age group from 1 month to 16 years were included, with a mean age of 10.81 years. Trauma was the commonest risk factor (40.9%), with unidentified foreign body fall being the most common (32.3%). No predisposing factors were identified in 50% of cases. Also, 36.8% of eyes were culture positive, with bacterial isolates in 17.9% and fungus in 82.1%. Moreover, 7.1% eyes were culture positive for Streptococcus pneumoniae and Pseudomonas aeruginosa each. Fusarium species (67.8%) was the commonest fungal pathogen, followed by Aspergillus species (10.7%). Also, 11.8% were clinically diagnosed as viral keratitis. No growth was found in 63.2% of patients. Treatment with broad-spectrum antibiotics/antifungals was administered in all cases. At the final follow-up, 87.8% achieved a best corrected visual acuity (BCVA) of 6/12 or better. Therapeutic penetrating keratoplasty (TPK) was required by 2.6% of eyes. Conclusion: Trauma was the major cause for pediatric keratitis. Majority of the eyes responded well to medical treatment, with only two eyes needing TPK. Early diagnosis and prompt management helped majority of the eyes to achieve a good visual acuity after the resolution of keratitis.

Transcriptome Analysis of Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.

Our previous studies have shown that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice spread to the eye with subsequent establishment of latency in choroid/RPE. In this study, RNA sequencing (RNA-Seq) analysis was used to determine the molecular genetic changes and pathways affected by ocular MCMV latency. MCMV (50 pfu per mouse) or medium as control were injected intra-peritoneally (i.p.) into BALB/c mice at <3 days after birth. At 18 months post injection, the mice were euthanized, and the eyes were collected and prepared for RNA-Seq. Compared to three uninfected control eyes, we identified 321 differentially expressed genes (DEGs) in six infected eyes. Using the QIAGEN Ingenuity Pathway Analysis (QIAGEN IPA), we identified 17 affected canonical pathways, 10 of which function in neuroretinal signaling, with the majority of DEGs being downregulated, while 7 pathways function in upregulated immune/inflammatory responses. Retinal and epithelial cell death pathways involving both apoptosis and necroptosis were also activated. MCMV ocular latency is associated with upregulation of immune and inflammatory responses and downregulation of multiple neuroretinal signaling pathways. Cell death signaling pathways are also activated and contribute to the degeneration of photoreceptors, RPE, and choroidal capillaries.

Corneal Transplantation for Infectious Keratitis: A Prospective Dutch Registry Study.

PURPOSE: The aim of this study was to analyze real-world practice patterns and graft survival after corneal transplantation for infectious keratitis in the Netherlands. METHODS: All consecutive keratoplasties for infectious keratitis registered in the Netherlands Organ Transplant Registry were included. Graft survival was analyzed using Kaplan-Meier survival curves with Cox regression to compare the 3 most common pathogens with subgroup analysis for type and reason of transplantation, sex, and graft size. Multivariable analysis was performed using the same explanatory factors. RESULTS: Between 2007 and 2017, 1111 keratoplasties for infectious keratitis were registered in the Netherlands Organ Transplant Registry. The most common pathogens were viruses (n = 437), bacteria (n = 271), and Acanthamoeba (n = 121). Human leukocyte antigen (HLA) matching did not provide a significant survival benefit, whereas emergency procedures showed worse graft survival [hazard ratio (HR) = 0.40, P = 0.120; HR = 2.73, P < 0.001, respectively]. Graft size >8.5 mm was significantly worse than graft size 8.5 mm (HR = 2.062, P = 0.010). In therapeutic keratoplasty, graft survival was significantly worse for Acanthamoeba than viral keratitis (HR = 2.36, P = 0.008). In the multivariable model, adjusting for graft size, type, and reason for transplantation, viral and bacterial keratitis did not differ significantly in graft survival, and Acanthamoeba showed a significantly worse prognosis (vs. viral keratitis, HR = 2.30, P < 0.001; bacterial keratitis, HR = 2.65, P < 0.001). CONCLUSIONS: Viral keratitis was the most common indication for transplantation, followed by bacterial and Acanthamoeba keratitis. HLA matching did not offer protection over elective non-HLA-matched procedures, whereas emergency procedures and grafts sized >8.5 mm showed poor survival. In optical keratoplasty, survival is high for all pathogens, whereas in therapeutic keratoplasty Acanthamoeba shows poor outcome.

Correlation of Adenoviral Titers with Severity of Adenoviral Conjunctivitis and Time to Viral Clearance for 21 Days.

SIGNIFICANCE: This investigation reports the correlation of conjunctival viral titers in adenoviral conjunctivitis with patient-reported symptoms and clinician-graded signs for 21 days of follow-up. PURPOSE: Adenoviral conjunctivitis is a highly contagious viral eye infection with significant morbidity and economic impact. This study investigates whether severity of signs and symptoms and time to viral clearance are correlated with conjunctival viral titers at baseline and during 21 days of follow-up. METHODS: The Reducing Adenoviral Patient Infected Days study was a pilot study of the efficacy of a single in-office administration of ophthalmic 5% povidone-iodine. This article outlines longitudinal analyses after the primary outcome report. Of 212 participants screened, 28 participants with quantitative polymerase chain reaction-confirmed adenoviral conjunctivitis were randomized and had follow-up visits on days 1, 2, 4, 7, 14, and 21. At each visit, clinician-graded signs, participant-reported symptoms, and a conjunctival swab for quantitative polymerase chain reaction analysis were obtained. The correlation of viral titers with symptoms and signs was calculated: (1) cross-sectionally at each visit and (2) longitudinally for 21 days using a repeated-measures mixed-effects model. RESULTS: Twenty-five of 28 participants had sufficient data for this report. Higher viral titers for 21 days were correlated with greater severity of symptoms (tearing, matting, and redness, r ≥ 0.70; P < .02) and greater severity of clinical signs (bulbar redness and serous discharge, r ≥ 0.60; P < .01). Eyes with highest baseline viral titers required longer time to viral clearance ( r = 0.59, P = .008). Signs and symptoms persisted in approximately half of the eyes even after viral clearance. CONCLUSIONS: Higher conjunctival viral titers across 21 days were strongly correlated with more severe signs and symptoms and longer time to viral clearance. Our results also indicate that symptoms and signs can persist after viral clearance.

Cytomegalovirus Anterior Uveitis: Clinical Manifestations, Diagnosis, Treatment, and Immunological Mechanisms.

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.