Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2 (PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs. METHODS: Tear samples were collected from 36 non-Sjögren syndrome dry eye patients (10 males and 26 females, mean age 50.11±11.17y). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time (TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay (ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction (MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores (R=0.608, P<0.001), however, they did not significantly associate with TBUT (R=0.153, P=0.373), Schirmer scores (R=-0.098, P=0.570), ocular surface staining scores (R=0.282, P=0.095), and stage of MGD (R=-0.107, P=0.535). Male sex was significantly negatively correlated with tear PGE2 levels. CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.     

Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca

PURPOSE: To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). METHODS: Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of botulinum toxin B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were subjected to an air blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under cobalt blue light with a digital camera fitted with a macro lens. RESULTS: BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to be an additional effect of the blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of both saline-injected and BTX-B-injected animals. CONCLUSIONS: Intralacrimal gland injection of BTX-B resulted in persistent corneal fluorescein staining within 3 days, and a significant decrease in aqueous tear production that persisted for 1 month. Intralacrimal gland injection of BTX-B suppressed lacrimation, thereby establishing a dry eye state. This animal model could be a useful tool for investigating the pathogenesis of the chronic condition KCS in humans.     

Restrictive lung disease and serum TGF-beta1 in thalassemia major children

A cross sectional study was performed in 21 thalassemia major (TM) children at King Chulalongkorn Memorial Hospital during March to August, 2003 to determine whether restrictive lung disease (RLD) was related to serum transforming growth factor-beta 1 (TGF-beta1). All studied patients (57% female, age 11.2 +/- 2.6 yrs, duration of transfusion 7.7 +/- 4.1 yrs) never had desferoxamine treatment and their pulmonary function, serum ferritin and serum TGF-beta1 were evaluated. Five (24%) had RLD. RLD patients had significantly longer durations of transfusion and higher serum ferritin levels than non-RLD patients (9.1 +/- 1.9 vs 5.5 +/- 3.2 yrs; p = 0.03 and 3,816.6 +/- 1,715.9 vs 2,084.5 +/- 1,504.8 ng/ml; p = 0.04, respectively). TM children had lower serum TGF-beta1 levels than normal children (7.9 vs 78.8 pg/ml; p < 0.001). The serum TGF-beta1 level was not different between RLD and non-RLD patients (13.3 vs 4.2 pg/ml; ns), concluding that RLD was related to longer duration of transfusion and higher serum ferritin but not related to serum TGF-beta1 levels.     

TFOS DEWS II Epidemiology Report

The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.     

Treatment With Intrastromal and Intracameral Voriconazole in 2 Eyes With Lasiodiplodia theobromae Keratitis: Case Reports

To report the clinical presentation and the role of intrastromal and intracameral voriconazole injection in the management of rare cases of fungal keratitis caused by Lasiodiplodia theobromae.Two eyes of 2 patients with Lasiodiplodia keratitis unresponsive to topical and oral antifungal medications were included in this study. Diagnosis of Lasiodiplodia keratitis was confirmed by microbiological analysis, including culture-based (case 1 and 2) and DNA sequencing techniques (case 2 only).The first patient presented with multiple satellite lesions and one of these infiltrates spread deeply into the cornea, forming a stromal abscess. Another patient had a large full-thickness corneal infiltrates with several fungal balls in the anterior chamber, requiring a limbus-to-limbus therapeutic penetrating keratoplasty. Despite aggressive topical therapy, the stromal abscess continued to worsen in the first case and recurrent keratitis was observed postoperatively in the second case. Voriconazole 50 μg/0.1 mL was administered intracamerally and intrastromally around the fungal abscess as adjuncts to topical antimycotics in the first case. The second patient who needed therapeutic keratoplasty was treated with an intracameral injection of 50 μg/0.1 mL voriconazole at the end of surgery. Postoperatively, 100 μg/0.1 mL voriconazole was also injected intracamerally after the recurrence of infection was noted in the graft. Reinjections were given 48 hours apart in both cases. After the injections, all corneal and anterior chamber lesions were reduced in size and density and completely resolved within 4 weeks.Intrastromal and intracameral voriconazole injections may offer safe and effective treatment options for L theobromae keratitis.     

Effect of topical olopatadine and epinastine in the botulinum toxin B-induced mouse model of dry eye.

PURPOSE: The aim of this study was to compare the effect of topical olopatadine, epinastine, and lubricant eye drops on dry eye ocular surface disease in the botulinum toxin B (BTX-B)-induced mouse model of keratoconjunctivitis sicca. METHODS: CBA/J mice were randomized into 3 experimental groups of 10 animals each. All mice received a transconjunctival injection of 0.05 mL of 20-mU BTX-B solutions into the left lacrimal gland. Three (3) days after intralacrimal gland injections, each group received treatment with twice-daily topical lubricant as a control, 0.1% olopatadine, or 0.05% epinastine eye drops. To monitor the progression of dry eye tear production, an ocular surface fluorescein staining score was evaluated in each of the 3 experimental groups. RESULTS: Three (3) days after the intralacrimal gland injection of BTX-B, aqueous tear production was significantly decreased (1.95+/-0.64 mm), compared to baseline level (2.69+/-0.66 mm; P<0.001). Similarly, there was a statistically significant increase in the proportion of mice with a corneal staining score of 2 or greater at 3 days postinjection, compared to the preinjection value (P<0.001). There were no statistically significant differences in aqueous tear production between the 3 different medication groups at all time points. Aqueous tear production in neither the olopatadine nor the epinastine-challenged groups was further decreased compared to the lubricant-treated group. Difference in the proportion of mice with a low- and high corneal staining score between the control and study groups did not reach statistical significance throughout the 4-week experimental period. In addition, changes in corneal fluorescein staining of the olopatadine group versus the epinastine group did not show a statistically significant difference. CONCLUSIONS: Topical olopatadine and epinastine do not cause significantly additional damage to the compromised ocular surface secondary to dry eye after continuous 4-week, twice-daily application. Topical olopatadine and epinastine appear to have comparable effects on aqueous tear-production and corneal-surface changes in this mouse model.