SARS-CoV-2 and the Eye: The Pandora's Box of Ocular Immunology.

The Pandora's box myth addresses the evilness in the world that undisputedly nowadays is identified in severe acute respiratory syndrome (SARS)-Coronavirus 2 (CoV-2), formerly known as Covid-19, which belongs to coronaviridae family, identified in Wuhan, Hubei district of the Republic of China in December 2019. Since then, SARS-CoV-2 has affected ∼180 million people and made almost 4 million victims, with a mortality rate of 6.1%, which is 6 times higher than influenza virus. However, coronaviruses are well known in the ophthalmology field because they were used in the so-called experimental coronavirus retinopathy model. That model certainly brings intriguing concepts for understanding coronavirus pathophysiology, which may have important implications on treatment strategies. Certainly, the recent availability of vaccines gives hope on the control of virus spreading; however, vaccines might create immune reactions involving the eye structure. In this study, we reviewed the literature and elaborated the available data to speculate on possible new interpretation of both pathophysiology and treatment of SARS-CoV-2.

Corneal Involvement in HIV-infected Individuals.

Corneal involvement in HIV-infected individuals may be broadly classified into two categories, namely, infectious and noninfectious with the vast majority of manifestations occurring in the former. In this article, we shall focus on these two categories and strive to highlight those presentations that should alert the clinician to suspect underlying HIV infection. Infectious group mainly consists of Herpitic group of viral infections. Bacterial causes may be due to Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeroginosa, alpha hemolytic Streptococcus, Micrococcus and Bacillus. Fungalf keratitis in HIV-infected individuals depends on the geographic locations from which patient comes. Microsporidia and Acanthamoeba are common Protozoal causes. Non-infective inflammatory causes include peripheral ulcerative keratitis, keratoconjunctivitis sicca, and squamous cell carcinoma of the conjunctiva. Severity which is abnormally severe or very minimally reactive makes the clinician suspect of immunosuppression.

Ocular Manifestations of Mosquito-Transmitted Diseases.

Of the 3,548 known mosquito species, about 100 transmit human diseases. Mosquitoes are distributed globally throughout tropical and temperate regions where standing water sources are available for egg laying and the maturation of larva. Female mosquitoes require blood meals for egg production. This is the main pathway for disease transmission. Mosquitoes carry several pathogenic organisms responsible for significant ocular pathology and vision loss including West Nile, Rift Valley, chikungunya, dengue viruses, various encephalitis viruses, malarial parasites, Francisella tularensis, microfilarial parasites, including Dirofilaria, Wuchereria, and Brugia spp., and human botfly larvae. Health care providers may not be familiar with many of these mosquito-transmitted diseases or their associated ocular findings delaying diagnosis, treatment, and recovery of visual function. This article aims to provide an overview of the ocular manifestations associated with mosquito-transmitted diseases.

[Mixed infections and inflammatory ophthalmic diseases: clinical and laboratory observations]. / Mikst-infektsii i vospalitel'naia oftal'mopatologiia: kliniko-laboratornye nabliudeniia.

In recent years, all medical specialists, including ophthalmologists, have been facing the problem of mixed infections. Recurrent inflammation in the anterior and posterior eye segments is often a result of infection by more than one variety of pathogens. MATERIAL AND METHODS: Over the period 2013-2016, 34 patients (14 men and 20 women) with different inflammatory processes in the eye who appeared DNA-positive for mycoplasmas (Mycoplasma hominis, Ureaplasma urealyticum) and/or chlamydiae (Chlamydia trachomatis) (PCR testing of tear fluid and/or urine) were followed up. All patients were examined for intensive production of herpesvirus, adenovirus, and enterovirus DNA in biological fluids. After being consulted by related specialists, all the patients started local and systemic (antibacterial and antiviral) therapy. In the end of the latter, laboratory tests were repeated. RESULTS: Among all the clinical forms, anterior segment inflammation (i.e. of conjunctiva, cornea, and the anterior vascular tract) prevailed - 76%. In most patients, mycoplasmas and/or chlamydiae formed associations with herpesviruses (n=19; 56%). Bacterial DNA alone (mycoplasma and/or chlamydia) was detected in 12 cases (35%). In 4 cases, mycoplasma and/or chlamydia DNA was detected in tear fluid, in 19 patients - in urine, and in 10 patients - in both secreta. Local and systemic causal treatment enabled resolution of the complaints and symptoms and yielded negative results of follow-up laboratory tests. CONCLUSION: More than a half of the patients demonstrated concomitant viral-bacterial infection (22 cases). The presence of bacterial/viral DNA in biological secreta, as revealed by PCR, reflects the systemic nature of the infection process and, thus, necessitates engagement of related specialists (dermatologists, urologists, gynecologists).

Association Between Visual Function Response and Reduction of Inflammation in Noninfectious Uveitis of the Posterior Segment.

Purpose: To examine the association between visual function response (VFR) and inflammation reduction in active noninfectious uveitis of the posterior segment (NIU-PS). Methods: Phase 3 SAKURA Study 1 randomized 347 subjects in a double-masked fashion to receive injections of intravitreal sirolimus 44 µg (n = 117); 440 µg (n = 114); or 880 µg (n = 116) every other month. Vitreous haze (VH) response, a measure of inflammation reduction, was defined as a VH score of 0 or 0.5+ at month 5 based on the modified Standardized Uveitis Nomenclature Scale. Visual function was assessed with best-corrected visual acuity (BCVA) and the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25). In this post-hoc analysis, principal component analysis was used to reduce the information in the multidimensional visual function outcome to a restricted number of independently relevant VFR measures. Minimal clinically important differences (MCID) for the VFQ-25-derived components were based on the standard error of measurements. Overall VFR was defined as either a BCVA improvement of ≥2 lines, or an improvement exceeding the MCID in the VFQ-25 based visual function measures. Results: The VFQ-25 composite score (VFQCS) and mental health subscale score (VFQMHS) were retained as relevant VFRs, with MCIDs of 4.3 and 11.7 points, respectively. A vitreous haze response was significantly associated with each VFR measure: VFQCS (odds ratio [OR] = 2.23; P = 0.0004); VFQMHS (OR = 2.84; P < 0.0001); BCVA (OR = 2.60; P = 0.0009), and overall VFR (OR = 2.65; P < 0.0001). Conclusions: Inflammation reduction to a VH score of 0 or 0.5+ was significantly associated with improved visual function. Achieving a VH response of 0 or 0.5+ is a patient-relevant outcome.

Intravitreal Adalimumab in Active Noninfectious Uveitis: A Pilot Study.

PURPOSE: To evaluate the short-term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis. METHODS: Consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2, then every 4 weeks for total of 26 weeks. RESULTS: Six out of 7 patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Seven out of 12 eyes had improvement of ≥2 ETDRS lines. Three out of three eyes had resolution of anterior chamber cells. And 9 of 10 eyes with vitreous haze had zero haze at 26 weeks. Five out of 8 eyes with macular edema had complete resolution. Median fluorescein angiography score improved from 14 to 4 on last follow-up. CONCLUSIONS: IVA was effective in controlling the inflammation, decreasing the macular edema, and improving the best corrected visual acuity in the majority of eyes in this series.

Infectious Keratitis Following Corneal Crosslinking: A Systematic Review of Reported Cases: Management, Visual Outcome, and Treatment Proposed.

AIM: To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment proposed. METHODS: A Medline (National Library of Medicine, Bethesda, MD, USA) search from October 2000 to October 2013 was performed to identify all articles describing infectious keratitis following corneal crosslinking treatment. Nineteen articles were selected. Ten articles reported infectious complications of corneal crosslinking treatment were included. Nine articles were excluded, because seven described sterile keratitis, one article was in German, and one reported general complication without describing the infection complication. RESULTS: A total number of infections reported included 10 eyes. The infectious keratitis was associated with bacteria in five eyes (50%): gram-positive bacteria in three eyes (30%) (staphylococcus epidermidis, S. aureus and streptococcus salivarius plus S. oralis, respectively) and gram-negative bacteria in two eyes (20%) (E. coli; P. aeruginosa); there was herpes virus in two eyes, fungus in two eyes (Fusarium and Microsporidia) (20%), and Acanthamoeba in one eye (10%). CONCLUSIONS: Only 10 cases of infectious keratitis following corneal crosslinking are published. The most virulent pathogens were Pseudomonas aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S. epidermidis. Two cases of herpes keratitis were described, suggesting the possibility of systemic antiviral prophylaxis before corneal crosslinking treatment. The most common risk factor of infections identified was postoperative incorrect patient behavior.

Comparison of two in situ corneal donation technique: morgue trephination or scleracorneal removal technique.

PURPOSE: To compare the two different 'in situ' methods of corneal trephination technique under morgue condition (morgue trephination technique, MTT) and classic scleracorneal removal technique (SRT). METHODS: A total of 1179 cases were evaluated for cornea donation at Gazi University Faculty of Medicine mortuary between the years 2008 and 2013 and were included to the study. Suitable donor corneas were retrieved with in situ trephination technique under morgue condition (group 1, MTT) or with in situ classic SRT (group 2, SRT). The two different 'in situ' methods were compared in terms of donor corneal biological quality (endothelial cell count, ECC) and functional outcome (presence of infection and primary graft failure). RESULTS: One hundred and fifty-two of 1179 cases were suitable for corneal donation. Two hundred and twenty-nine corneas of 152 cases were transplanted, 108 corneas were obtained with MTT and 121 corneas were obtained with SRT. Pretransplant and post-transplant ECCs were 2402.5 ± 115.6 and 2108.3 ± 108.23 (p = 0.065) in MTT, respectively, and 2512.7 ± 130.4 and 2235.4 ± 201.8 (p = 0.059) in SRT, respectively. The incidence of primary graft failure and infection was not statistically significantly different between two method [2.7% and 1.6% (p = 0.223), 0.9% and 0.8% (p = 0.115)]. CONCLUSION: The two different 'in situ' methods, MTT and SRT, were similar in terms of donor ECC, presence of infection and primary graft failure. Cornea excision performed through the technique described herein may increase the corneal donation rates as result of reduced disfigurement to donor body and offer important contributions during surgery with good anatomic adaptation of tissues.

Deep anterior lamellar keratoplasty using acellular corneal tissue for prevention of allograft rejection in high-risk corneas.

PURPOSE: To determine whether deep anterior lamellar keratoplasty (DALK) using acellular glycerol-cryopreserved corneal tissue (GCCT) could prevent allograft rejection in high-risk corneas. DESIGN: Prospective, randomized, comparative study. SETTINGS: The Eye Hospital, Wenzhou Medical College, Zhejiang, China. STUDY POPULATION: All patients with herpes simplex virus keratitis, bacterial keratitis, fungal keratitis, or ocular burn, who were eligible as per study design, were invited to participate. OBSERVATION PROCEDURES: According to randomized block design, all patients received either GCCT or fresh corneal tissue (FCT) during DALK. Best-corrected visual acuity (BCVA), slit-lamp microscopy, and in vivo confocal microscopy examinations at 1 week and 1, 3, 6, 12, and 24 months after surgery were analyzed. Kaplan-Meier survival analysis was used to evaluate graft survival rate. MAIN OUTCOME MEASURES: Therapeutic success, 2-year rejection-free graft survival rate and 2-year graft survival rate, in vivo confocal microscopy results, BCVA, and endothelial cell density. RESULTS: Postoperative BCVA of 20/40 or better at the last follow-up visit was achieved in 57.6% (19/33) of eyes in the GCCT group and in 54.8% (17/31) of the FCT group. No graft rejection occurred in the GCCT group, while in the FCT group 10 episodes of stromal rejection developed in 7 eyes. Overall, the rejection-free graft survival rate at 2 years was significantly higher in the GCCT group as compared with the FCT group (100.0%, 78.8% respectively, P = .006). CONCLUSIONS: Deep anterior lamellar keratoplasty using acellular glycerol-preserved cornea could prevent allograft rejection and promote graft survival rate in high-risk corneas.

Prototheca wickerhamii infection of a corneal graft.

Algae are generally noninfectious agents in mammals, with few known pathogenic algae. Prototheca is an achlorophylic nonphotosynthetic algae, globally ubiquitous, and readily isolated from rivers, lakes, ponds, and soil. Although canine and bovine protothecosis have been reported more widely, infections in humans are rare, particularly in patients with an intact immune system. The majority of protothecal infections in humans is associated with Prototheca wickerhamii. We report an unusual case of P. wickerhamii infection in an immunocompetent corneal transplant patient.

Sequential therapeutic penetrating keratoplasty with cryopreserved and fresh corneal tissue for severe infectious keratitis: a case-control study.

PURPOSE: Sequential therapeutic penetrating keratoplasty (TPK) using a cryopreserved cornea followed soon after by a fresh optical grade cornea for severe infectious keratitis may improve the survival of the optical graft. The aim of this study was to compare the therapeutic efficacy, visual outcomes, and graft survival for sequential TPK against TPK using a fresh optical grade cornea alone. METHODS: This was a retrospective case-control study. Case records were reviewed for clinical and surgical outcomes. RESULTS: Thirty-two eyes of 32 patients were included. Ten eyes underwent sequential TPK (TPK cases), and there were 22 age- and sex-matched controls, which underwent TPK with optical grade tissue alone. The mean interval between the TPK with the frozen cornea and the subsequent optical keratoplasty in the TPK cases was 16.8 ± 12.9 days. Therapeutic success, defined as the eradication of the primary infection, was achieved in all the TPK cases but only in 13 controls (59.1%) (P = 0.06). Graft survival at 1 year was better in the TPK cases than the controls (72.9% vs 53.8%). An improvement in Snellen acuity by at least 2 lines was more likely in the TPK cases than the controls (80% vs 14%; P = 0.001). CONCLUSIONS: Sequential TPK is an effective surgical therapy for active severe infectious keratitis and also helps to conserve valuable optical grade corneal tissue.

[Ophthalmological profile of patients living with HIV/AIDS].

INTRODUCTION: Serbia has 2.287 registered HIV positive persons. A certain number has ocular complications which are mainly the result of opportunistic infections accompanying this illness. Due to a highly stigmatizing environment for people living with HIV/AIDS in Serbia, they do not always seek doctors assistance despite the fear of losing their sight. CASE REPORT: We presented ophthalmologic status of nine HIV positive persons, all at the different phases of the illness. The decrease in the visual acuity was the first symptom which led to the diagnosis of HIV infection in two of our patients. CONCLUSION: Ophthalmologist has an important role in the multidisciplinary approach to patients with HIV/AIDS from introducing the diagnosis to the follow-up and the treatment of ocular complications which may accompany this chronic illness. With the active involvement of eye professionals serious consequences can be prevented, which have not only medical but also social and economic implications on the individual and the society as a whole.

Outcomes of therapeutic deep lamellar keratoplasty and penetrating keratoplasty for advanced infectious keratitis: a comparative study.

PURPOSE: To compare the therapeutic success, visual outcomes, complications, and graft survival rates of therapeutic deep anterior lamellar keratoplasty (TDALK) and therapeutic penetrating keratoplasty (TPK) for advanced infectious keratitis. DESIGN: Retrospective, comparative study. PARTICIPANTS: One hundred twenty-three patients (126 eyes) with medically uncontrolled infectious keratitis of bacterial, fungal, or acanthamoeba etiologies who underwent TDALK (n = 26) or TPK (n = 100 eyes; 80 nonperforated ulcers; 20 perforated ulcers; mean follow-up in TDALK, 12.9 months; in TPK, 21.3 months). METHODS: We performed TDALK for infections confined to the corneal stroma and the technique used was either manual lamellar dissection or Anwar's big bubble technique for total stromal removal. Therapeutic penetrating keratoplasty was performed for either nonperforated or perforated ulcers. Comparison with respect to recurrence of infection, visual acuity, graft survival, and complications was made. Baseline characteristics of the patients were analyzed using the chi-square test. Kaplan-Meier survival analysis was used to evaluate graft survival. MAIN OUTCOMES MEASURES: Therapeutic success (eradication of infection) or therapeutic failure (recurrence of original infection in cornea or sclera, or as endophthalmitis), graft survival (clarity), and best-corrected visual acuity (BCVA). RESULTS: Therapeutic success rate of 84.6% was achieved in the TDALK group and 88% in the TPK group (P = 0.74); of the 12 eyes with recurrence of infection in the TPK cohort, 6 developed endophthalmitis with poor outcomes. A BCVA of > or =6/9 was achieved in 50% of patients in the TDALK group and 20.2% in the TPK group (P = 0.01). Mean improvement of acuity was 7.27 lines in the TDALK group and 4.76 lines in the TPK group (P = 0.01). Kaplan-Meier survival analysis at 1 year showed better graft survival for TDALK (90%) compared with TPK (78.4%). CONCLUSIONS: For medically unresponsive infectious keratitis, TDALK may be considered instead of TPK yielding similar graft survival, without an increased risk of disease recurrence.

Toll-like receptors at the ocular surface.

The Toll-like receptor (TLR) family of pathogen recognition molecules has an important role in recognizing microbial pathogens and microbial breakdown products. Activation of TLRs in the corneal epithelium induces CXC chemokine production and recruitment of neutrophils to the corneal stroma. Although essential for pathogen killing, neutrophils can cause extensive tissue damage, leading to visual impairment and blindness. In this review, we examine the role of TLRs in microbial keratitis and in noninfectious corneal inflammation, most commonly associated with contact lens wear. we present recent findings on TLR signaling pathways in the cornea, including MyD88- and TRIF-dependent responses and discuss the role of resident macrophages and dendritic cells. Finally, we examine the potential for targeting the TLR pathway as a potential therapeutic intervention for microbial keratitis and contact lens-associated corneal inflammation.

Intraocular inflammation: its causes and investigations.

Intraocular inflammation, or uveitis, incorporates a diverse group of infectious and immune-mediated disorders. In addition, some conditions masquerade as uveitis. However, classifying uveitis according to anatomic location in adult and pediatric populations, and appreciating the effect of immune status and regional differences, refines the list of potential causes. In this way, a select few investigations can be performed, rather than a nondirected battery of tests.

Ocular infection and inflammation.

Managing the inflamed or infected eye in the emergency setting presents a diagnostic and therapeutic challenge to the emergency physician; the causes and prognoses range from benign, self-limited illness to organ-threatening pathology. A careful history, with attention to comorbid illnesses and time course, is paramount, as is knowledge of the complete ophthalmologic examination. Much of the organ morbidity is ameliorated with prompt therapy in the emergency department and by initiating ophthalmologic consultation. In this article, the authors discuss the diagnosis and treatment of several types of eye infection, including conjunctivitis, episcleritis, keratitis, uveitis, hordeolum and chalazion, dacryocystitis, and cellulitis.

Infectious and noninfectious keratitis after laser in situ keratomileusis Occurrence, management, and visual outcomes.

PURPOSE: To retrospectively review the occurrence, treatment, and visual outcomes associated with various etiologies of keratitis as a postoperative complication of laser in situ keratomileusis (LASIK) at an academic surgical center. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: The charts of 5618 post-LASIK patients (10 477 eyes) were reviewed for the development of keratitis. Occurrence rates, management regimens, and final best spectacle-corrected visual acuity (BSCVA) were reported for infectious and noninfectious keratitis etiologies. RESULTS: Post-LASIK keratitis was diagnosed in 279 eyes. The keratitis was diagnosed as infectious in 33 eyes (12%) and as noninfectious in 246 eyes (88%). Infectious cases included 5 eyes (15%) with herpes simplex keratitis (HSV), 18 (55%) with adenoviral keratitis, and 10 (30%) with nonviral (including bacterial, fungal, and parasitic) keratitis. Of noninfectious cases, 193 (78%) were classified as diffuse lamellar keratitis (DLK), 36 (15%) as staphylococcal marginal hypersensitivity, and 17 (15%) as localized debris-related keratitis. CONCLUSIONS: The occurrence of post-LASIK keratitis was 2.66%, with DLK being the most common diagnosis overall. The occurrence of noninfectious keratitis (2.34%) was 7.5 times greater than the occurrence of infectious keratitis (0.31%). Adenoviral keratitis had the best visual outcomes overall, with all 18 patients achieving 20/20 BSCVA. In contrast, all 5 eyes with HSV keratitis lost 1 or 2 lines of BSCVA. Excluding adenoviral keratitis, infectious etiologies had significantly worse visual outcomes than noninfectious etiologies at the 20/40 and 20/20 levels (P = .0013 and P<.001, respectively).

The eye in systemic infection.

Bacterial, fungal, viral, and parasitic pathogens all cause systemic infection and can spread to the eye. Dissemination of pathogens via the bloodstream can lead to direct involvement of the eye. Visual loss is common in bacterial or fungal endophthalmitis, and toxoplasmosis is a major cause of ocular morbidity and poor vision after congenital or acquired infection. Some infections cause intraocular damage by indirect mechanisms (eg, HIV-mediated immunosuppression), leading to opportunistic infections such as cytomegalovirus infection, periocular nerve involvement due to leprosy, and hypersensitivity reactions in tuberculosis. Eye symptoms might indicate the outcome of an underlying infection, such as development of retinal ischaemia in severe malaria, which is associated with a poor prognosis. Successful outcome for patients with ocular infection depends on close collaboration between clinicians identifying and treating underlying disease, specialist ophthalmic review, and ophthalmic interventional skills (when needed).

Estudo sobre as causas mais freqüentes de perdas oculares / A study on the most frequent causes of ocular losses

As perdas oculares são constrangedoras ao portador por comprometer a face que é parte do corpo humano que possue os órgãos essenciais para o relacionamento humano. Foram avaliados no presente estudo prontuários de 53 pacientes da clínica de prótese buco-maxilo-facial do Centro de Oncologia Bucal da UNESP de Araçatuba, que tiveram a região ocular comprometida, sendo classificadas em ordem de prevalência as causas das perdas oculares. O glaucoma foi responsável por 37 por cento das perdas oculares, seguido por traumas ou acidentes com 32 por cento. Muitas são as causas das perdas oculares, sendo o glaucoma o principal responsável. As próteses oculares foram criadas com o intuito de devolver a função e a estética comprometidas pela ausência de parte ou total do globo ocular