Vision Crisis-Bilateral Outer Retinitis Due to Mumps Virus.

PURPOSE: To report a case of mumps-associated outer retinitis, diagnostic, and therapeutic challenges associated with the disease. METHOD: Retrospective observational case report. RESULTS: An 8-year-old male child on presentation had a history of mumps infection following which he developed outer retinitis. Upon evaluation, he had bilateral multifocal perivascular cerebriform retinitis. MRI revealed increased uptake of contrast by bilateral parotid gland and with serum mumps IgM and IgG antibodies being raised, a diagnosis of mumps associated outer retinitis was made. In terms of treatment post-systemic steroid therapy, hyperbaric oxygen therapy was tried as a rescue therapy in this patient. Improvement in vision was noted in the left eye more than the right eye. CONCLUSION: Hyperbaric oxygen therapy can be considered as an additional therapy to systemic steroid therapy in mumps associated retinitis. In such a situation, since there is no specific antiviral drug available for mumps infection, the most effective treatment is prevention by vaccination.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Pemphigus and Pemphigoid.

PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon   and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.

Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. METHODS: Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. RESULTS: Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. CONCLUSIONS: Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Impact of Air Pollution on the Ocular Surface and Tear Cytokine Levels: A Multicenter Prospective Cohort Study.

Purpose: To assess air pollution-induced changes on ocular surface and tear cytokine levels. Methods: As a prospective multicenter cohort study, 387 dry eye disease (DED) participants were recruited from five provinces in China and underwent measurements of ocular surface disease index (OSDI), Schirmer's I test (ST), tear meniscus height (TMH), tear film break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland (MG) function, and tear cytokines. The associations between ocular surface parameters and exposure to particulate matter (PM), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2) for 1 day, 1 week, and 1 month before the examination were analyzed in single- and multi-pollutant models adjusted for confounding factors. Results: In the multi-pollutant model, the OSDI score was positively correlated with PM with diameter ≤2.5 µm (PM2.5), O3, and SO2 exposure [PM2.5: ß (1 week/month) = 0.229 (95% confidence interval (CI): 0.035-0.424)/0.211 (95% CI: 0.160-0.583); O3: ß (1 day/week/month) = 0.403 (95% CI: 0.229-0.523)/0.471 (95% CI: 0.252-0.693)/0.468 (95% CI: 0.215-0.732); SO2: ß (1 day/week) = 0.437 (95% CI: 0.193-0.680)/0.470 (95% CI: 0.040-0.901)]. Tear secretion was negatively correlated with O3 and NO2 exposures but positively correlated with PM2.5 levels. Air pollutants were negatively correlated with TBUT and positively related with CFS score. Besides SO2, all other pollutants were associated with aggravated MG dysfunction (MG expression, secretion, and loss) and tear cytokines increasement, such as PM2.5 and interleukin-8 (IL-8) [ß (1 day) = 0.016 (95% CI: 0.003-0.029)], PM with diameter ≤10 µm (PM10) and IL-6 [ß (1 day) = 0.019 (95% CI: 0.006-0.033)], NO2 and IL-6 [ß (1 month) = 0.045 (95% CI: 0.018-0.072)], among others. The effects of air pollutants on DED symptoms/signs, MG functions and tear cytokines peaked within 1 week, 1 month, and 1 day, respectively. Conclusion: Increased PM2.5, O3, and SO2 exposures caused ocular discomfort and damage with tear film instability. PM10 exposure led to tear film instability and ocular injury. PM, O3, and NO2 exposures aggravated MG dysfunction and upregulated tear cytokine levels. Therefore, each air pollutant may influence DED via different mechanisms within different time windows.

Correlations between tear fluid and aqueous humor cytokine levels in bullous keratopathy.

PURPOSE: To evaluate the correlation between tear fluid and aqueous humor (AqH) cytokine levels in eyes with bullous keratopathy (BK) and with normal endothelium. METHODS: This prospective consecutive case-series study included 71 eyes of 71 patients: 31 eyes with BK, 18 eyes with non-BK corneal diseases, and 22 eyes with uncomplicated cataract (healthy controls). Total protein and cytokine (interleukin [IL]-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, MIP-1α, MIP-1ß, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, soluble intercellular adhesion molecule [sICAM]-1, and IP-10) levels in the tear fluid and AqH were measured using multiplex beads immunoassay. The correlations between tear and AqH cytokine levels were assessed. RESULTS: The AqH protein level was significantly higher in BK eyes (1.09 ± 0.08 mg/mL) than in non-BK (0.63 ± 0.11, P = 0.0004) and healthy control (0.62 ± 0.06, P = 0.0002) eyes. The tear total protein and IL-4 levels were significantly higher in the BK group compared to healthy controls (P = 0.0374 and 0.0032, respectively). The AqH IL-8 and sICAM-1 levels were significantly higher in the BK group compared to controls (P = 0.0001 and 0.0083, respectively). In BK eyes, the tear IL-4 level was significantly correlated with the MCP-1(r = 0.563, P = 0.001) and total protein (r = 0.589, P = 0.001) AqH levels. The tear IL-8 level was significantly correlated with the MCP-1(r = 0.598, p = 0.001) and IL-4 (r = 0.781, p < 0.0001) AqH levels in BK eyes. However, no significant correlations were found between tear and AqH cytokine levels in non-BK and healthy controls eyes. CONCLUSIONS: The tear cytokine levels are correlated with those of AqH only in BK, but not in non-BK and healthy controls.

Tear cytokine profiling in patients with superior limbic keratoconjunctivitis who underwent medical treatment or in conjunction with surgical management.

PURPOSE: To determine the correlation between superior limbic keratoconjunctivitis (SLK) and selected tear cytokines and to evaluate the efficacy of these cytokines in monitoring the response of patients with SLK to either medical treatment alone or in combination with conjunctival resection. DESIGN: A cohort study. METHODS: Twenty-five eyes of 13 patients with SLK were assigned to either medically responsive or surgical treatment groups depending on their responses 1 month after initial medical treatment. Treatment efficacy was assessed by improvements in clinical grading and decreases in the levels of tear cytokines. RESULTS: Fourteen eyes were improved by medical treatment alone, whereas satisfactory outcomes were achieved for the remaining 11 eyes after surgical management. The overall grading prior to medical treatment was lower in medically responsive group compared with surgical treatment group (p=0.0139). Among the examined tear cytokines, monocyte chemoattractant protein (MCP)-1 was positively associated with the severity of clinical grading (p=0.0251). While both treatments significantly decreased the levels of MCP-1 and interleukin-6, surgical treatment also decreased the levels of interferon-γ and tumour necrosis factor-α. Notably, overall cytokine levels after surgical treatment were lower than those after medical treatment alone. CONCLUSIONS: Since an association of tear MCP-1 level with the clinical grading and treatment response of SLK was observed in this study, tear MCP-1 may be a potential indicator of SLK disease severity. According to the degree to which the tear cytokine levels were decreased, surgical treatment appears to be an effective treatment modality for patients with SLK who are refractory to medical treatment alone.

Non-invasive objective and contemporary methods for measuring ocular surface inflammation in soft contact lens wearers - A review.

Contact lens wear is one of the primary risk factors for the development of ocular surface inflammatory events. The purpose of this review is to examine and summarize existing knowledge on the mechanisms of contact lens related ocular surface inflammation and the evidence for the effectiveness of current objective methods to measure ocular surface inflammation. Contact lens wear is postulated to trigger an inflammatory response on the ocular surface due to mechanical, chemical, hypoxic stress, or by the introduction of microbes and their toxins. Apart from the traditional signs of inflammation, such as swelling, oedema, redness and heat, on the ocular surface, other methods to measure ocular surface inflammation in sub-clinical levels include tear inflammatory mediator concentrations, conjunctival cell morphology, and corneal epithelial dendritic cell density and morphology. Tear inflammatory mediator concentrations are up- or down-regulated during contact lens wear, with or without the presence of associated inflammatory events. There is higher conjunctival cell metaplasia observed with contact lens wear, but changes in goblet cell density are inconclusive. Dendritic cell density is seen to increase soon after initiating soft contact lens wear. The long term effects of contact lens wear on dendritic cell migration in the cornea and conjunctiva, including the lid wiper area, require further investigation. Currently patient factors, such as age, smoking, systemic diseases and genetic profile are being studied. A better understanding of these mechanisms may facilitate the development of new management options and strategies to minimize ocular surface inflammation related to contact lens wear.

Meibomian gland dysfunction and tear cytokines after cataract surgery according to preoperative meibomian gland status.

BACKGROUND: To investigate the possible mechanisms by which cataract surgery aggravates meibomian gland dysfunction (MGD), we evaluated the changes in tear cytokines and ocular surface parameters after cataract surgery according to the preoperative MGD grade. DESIGN: Prospective, observational case series. PARTICIPANTS: A total of 50 eyes from 50 patients who underwent cataract surgery were included. METHODS: Patients were classified into two groups: Group I had no or minimal MGD, and group II had grades 2-4 MGD. Ocular surface parameters were measured, including tear film break-up time, Schirmer I test, ocular surface staining and Ocular Surface Disease Index, and tear cytokine levels were measured. MAIN OUTCOME MEASURES: The main outcomes were changes in ocular surface parameters and inflammatory tear cytokine concentrations. RESULTS: In group II, preoperative MGD grade, ocular surface staining, tear film break-up time and Ocular Surface Disease Index were worse, and mean interleukin (IL)-2, IL-6 and TNF-α levels were higher than those of group I. MGD and ocular surface parameters were worsened to a greater degree after surgery in group II than in group I (P < 0.050). In group II, IL-6 and TNF-α levels significantly increased at postoperative 1 month, and there were significant correlations between changes in ocular surface parameters and tear cytokines (IL-2, IL-6 and TNF-α; P < 0.050). CONCLUSIONS: The extent to which the MGD grade was aggravated following cataract surgery differed based on preoperative MGD grade. Preoperative MGD and ocular surface status should be carefully evaluated.

Tear cytokine profile as a noninvasive biomarker of inflammation for ocular surface diseases: standard operating procedures.

PURPOSE: To provide standard operating procedures (SOPs) for measuring tear inflammatory cytokine concentrations and to validate the resulting profile as a minimally invasive objective metric and biomarker of ocular surface inflammation for use in multicenter clinical trials on dry eye disease (DED). METHODS: Standard operating procedures were established and then validated with cytokine standards, quality controls, and masked tear samples collected from local and distant clinical sites. The concentrations of the inflammatory cytokines in tears were quantified using a high-sensitivity human cytokine multiplex kit. RESULTS: A panel of inflammatory cytokines was initially investigated, from which four key inflammatory cytokines (IL-1ß, IL-6, INF-γ, and TNF-α) were chosen. Results with cytokine standards statistically satisfied the manufacturer's quality control criteria. Results with pooled tear samples were highly reproducible and reliable with tear volumes ranging from 4 to 10 µL. Incorporation of the SOPs into clinical trials was subsequently validated. Tear samples were collected at a distant clinical site, stored, and shipped to our Biomarker Laboratory, where a masked analysis of the four tear cytokines was successfully performed. Tear samples were also collected from a feasibility study on DED. Inflammatory cytokine concentrations were decreased in tears of subjects who received anti-inflammatory treatment. CONCLUSIONS: Standard operating procedures for human tear cytokine assessment suitable for multicenter clinical trials were established. Tear cytokine profiling using these SOPs may provide objective metrics useful for diagnosing, classifying, and analyzing treatment efficacy in inflammatory conditions of the ocular surface, which may further elucidate the mechanisms involved in the pathogenesis of ocular surface disease.

Clinical and immunological responses in ocular demodecosis.

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1ß, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1ß in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1ß and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.