Background and Aims Several studies in the past have attempted to demonstrate the efficacy of sodium hyaluronate in the treatment of xerophthalmia. However, results have been conflicting and a definite conclusion has not yet been reached. In order to provide integrated evidence for the effectiveness of sodium hyaluronate and to judge the methodological value of relevant randomized controlled trials (RCTs) in nearly thirty years, we conducted this meta-analysis. Methods A range of electronic databases were searched: MEDLINE, the Cochrane Library Database, EMBASE, CINAHL, Web of Science and the Chinese Biomedical Database (CBM) without language restrictions. Two independent reviewers assessed trials for eligibility and quality, and meta-analysis was performed using the STATA 12.0 software. Integrated odd ratio (OR) with its corresponding 95% confidence interval (95%CI) was calculated. Results Six RCTs were included with a total of 839 xerophthalmia patients. The meta-analysis results revealed that patients with xerophthalmia who received the intervention of sodium hyaluronate eye drops didn't have significantly higher remission rate of dry eye symptoms than those in controlled groups (OR = 1.811, 95% CI = 0.741∼4.429, p = 0.193). Sensitivity analysis suggested the statistical results were robust. No publication bias was detected in this meta-analysis (P>0.05). Conclusion Although sodium hyaluronate can be used to help relieve the symptoms of dry eyes, present evidences cannot show in unequivocal terms that patients with xerophthalmia can benefit more from the clinical application of sodium hyaluronate than other eye drops or therapies.

The value of biannual distribution of 200,000 IU of vitamin A in preventing xerophthalmia was assessed in a randomized, controlled community-based trial involving 25,000 preschool children in 450 villages of northern Sumatra. Results indicate that distribution was associated with a dramatic decline in xerophthalmia prevalence; that concurrent controls were critical for distinguishing spontaneous from program-related changes; and that the apparent level of benefit depended on the choice of clinical indicator(s). Night blindness ceases to be an accurate reflection of impact when prevalence rates are low, and comparison of Bitot's spot rates should be confined to new cases of disease.

PURPOSE: To assess the impact of vitamin A supplementation at 4-month intervals on the prevalence and incidence of xerophthalmia among preschool-age children. METHODS: A stratified, random sample of 40 wards with 4766 children in Sarlahi district of Nepal was selected to participate in a randomized, controlled, community trial. In the vitamin A group, at 4-month intervals, neonates received 50,000 IU, 1- to 11-month-old infants received 100,000 IU, and children 1 through 4 years of age received 200,000 IU. Children underwent eye examination before the intervention and 16 months later. RESULTS: Before the intervention, 4318 children were examined for xerophthalmia. The prevalence was 2.3% in the vitamin A group and 3.3% in the placebo group. All children with xerophthalmia were treated with vitamin A at the time of the examination. Of those examined at baseline, 38 in the vitamin A group and 48 in the placebo group died in the 16 months after intervention. There were 1871 (84%) surviving children in the vitamin A group and 1711 (85%) in the placebo group examined at follow-up. After adjustment for the baseline prevalence of xerophthalmia, vitamin A reduced the prevalence at follow-up by 63% (95% confidence interval, 21% to 83%). The apparent incidence was 3.2/1000 per year in the vitamin A group and 9.2/1000 per year in the placebo group, an adjusted reduction of 62% (95% confidence interval, 0% to 86%). CONCLUSIONS: Supplementation was effective at reducing the prevalence and incidence of xerophthalmia.

We examined the effect of 60-mg (200,000-IU) supplements of vitamin A administered every 6 mo on the incidence of xerophthalmia among preschool children who were free of eye symptoms and signs of vitamin A deficiency. We also prospectively studied the relationship of dietary vitamin A intake with the same endpoint. After 18 mo of follow-up, 400 children developed xerophthalmia during 80,104 child-periods of follow-up. Vitamin A supplementation only modestly reduced the risk of xerophthalmia (relative risk 0.88, 95% confidence interval 0.72-1.07, P = 0.19). On the other hand, total dietary vitamin A intake was strongly associated with reduced risk of xerophthalmia; the multivariate relative risk when children in extreme quintiles were compared was 0.38 (95% confidence interval 0.19-0.74; P for trend over quintiles = 0.002). These results emphasize the need for further data on factors that modify the bioavailability of large-dose vitamin A supplements. Increased consumption of inexpensive vegetables and fruits is highly likely to reduce significantly the risks of vitamin A deficiency, including nutritional blindness in developing countries.

A randomized, double-masked, placebo-controlled clinical trial was conducted with 236 preschool children, age 3-6 y, in Indonesia to assess immune status in mild vitamin A deficiency. The immune response to tetanus immunization was used as a measure of immune competence. Clinically normal children (n = 118) and children with mild xerophthalmia (n = 118) were randomly assigned to receive oral vitamin A (60,000 micrograms retinol equivalent) or placebo treatment for a total of four study groups. Two weeks after treatment, children were immunized with diphtheria-pertussis-tetanus vaccine. The immunoglobulin G (IgG) responses to tetanus at baseline and 3 wk following immunization were measured by ELISA. After adjusting for previous tetanus immunization, clinically normal and xerophthalmic children receiving vitamin A had a significantly greater IgG response to tetanus than clinically normal and xerophthalmic children receiving placebo (P less than 0.05). These results suggest that children with mild vitamin A deficiency have a relative immune depression compared with children who have been supplemented to normal vitamin A levels.

Xerophthalmia has been found to be an important cause of blindness in the Philippines. An earlier study had investigated its prevalence and epidemiology on the island of Cebu. The research now presented consists of an evaluation of the relative effectiveness of three different intervention strategies to control vitamin A deficiency in Cebu. These interventions were 1) a public health and horticulture intervention, 2) the provision of 200,000 IU of vitamin A to children every 6 months (the "capsule intervention"), and 3) the fortification of monosodium glutamate with vitamin A. A total of 12 areas or barangays were included. Each intervention was monitored in four different barangays, two urban and two rural, for almost 2 years. Similar examinations were performed before and after the interventions. The monosodium glutamate fortification was the only intervention that resulted both in a significant reduction in clinical signs of xerophthalmia and in a significant rise in serum vitamin A levels. Fortification is now being planned in three Philippine provinces.

Inconsistencies have been observed in the impact of vitamin A (VA) supplementation on early child growth. To help clarify this issue, a cohort of 3377 rural Nepalese, nonxerophthalmic children 12-60 mo of age were randomized by ward to receive vitamin A [60,000 microg retinol equivalents (RE)] or placebo-control (300 RE) supplementation once every 4 mo and followed for 16 mo. VA had no impact on annual weight gain or linear growth. However, arm circumference (AC) and muscle area (MA) growth improved in VA recipients, by 0.13 cm and 25 mm2, respectively, over controls. Growth of children with xerophthalmia, who were treated with >/= 120, 000 RE at base line, was also compared to that of nonxerophthalmic children, stratified by initial wasting status, and adjusted for sex, baseline age and measurement status. Among initially nonwasted children (AC >/= 13.5 cm), VA-treated xerophthalmic children (n = 86) gained 0.7 cm more in linear growth than nonxerophthalmic children. Among initially wasted children (AC < 13.5 cm), VA-treated children (n = 34) gained additional weight (672 g), height (approximately 1 cm), muscle (76 mm2) and fat (79 mm2) areas, and subscapular skinfold (1.3 mm) compared to changes observed in nonxerophthalmic children. Relative increments in soft tissue growth occurred within 4 mo of VA treatment, while the effect on linear growth was gradual. Moderate-to-severe VA deficiency, marked by xerophthalmia, is likely to impair normal physical growth, but milder stages of deficiency may not have this effect in rural South Asia.

OBJECTIVE: To study the validity of saliva ferning patterns as a diagnostic test for dry mouth in primary or secondary Sjogren's Syndrome (SS). METHODS: Salivary smears were collected from 25 patients with Sjögren's syndrome in the fasting and nonfasting state. All 25 patients had symptomatic xerostomia and xerophthalmia and a positive Shirmer's test. Smears were taken from four sites, the cheek, lower lip, tongue, and saliva. Tests were done for rheumatoid factor, antinuclear antibodies, and anti-Ro(SS-A) antibodies. The salivary smears were air-dried and examined under a light and a polarizing microscope. Smears from 25 healthy subjects were also examined as controls. RESULTS: Three patterns of salivary secretion were identified, namely normal geometric ferning, reindeer antler ferning, and thick branching ferning. All Sjögren's syndrome patients had abnormal salivary smears, usually with a combination of reindeer antler ferning, thick branching ferning, and mucosal squames. This combination was seen in six of the 25 fasting specimens (24%); most of the remaining fasting samples showed the reindeer antler ferning. Reindeer antler ferning alone was found in five fasting and four nonfasting samples: this pattern was absent from five fasting and five nonfasting samples in which mucosal squames were the only abnormal finding. All nonfasting control samples exhibited normal geometric ferning. Smears from the cheek and saliva provided the most illustrative findings. CONCLUSION: The saliva ferning test is a simple, reproducible, and useful diagnostic aid in autoimmune xerostomia, approximately equivalent to Shirmer's test in xerophthalmia.

A double blind study conducted during January 90–March 91 in a rural part of Varanasi district in Uttar Pradesh state of India on 9987 and 5260 children under six years of age demonstrated that administration of vitamin A reduced overall mortality by 14.0%. The additional data collected from January 1991 to February 92 under similar settings on 1314 and 1200 children of same age in the experimental and control groups respectively and from all children suffering from xerophthalmia who received mega dose of vitamin A (200,000 I.U.), taken together, show that vitamin A supplementation results in 16.9% reduction in mortality. Mortality was reduced in unimmunized children by 22.0%, diarrhea by 18.8% and measles by 9.0%. However, significant reduction in mortality in vitamin A supplemented group was observed only for deaths due to severe malnutrition. No death was recorded in xerophthalmia children who received mega dose of vitamin A (200,000 I.U.). The child survival pattern remained unaltered and mortality pattern remained unchanged significantly even after one year of withdrawal, thus denying the possibility of any substantial change in the study area for births and deaths. Thus the finding that vitamin A supplementation protects against overall mortality and in particular deaths due to gastroenterits, severe malnutrition and in unimmunized children is of significance.

Vitamin A has been determined in tear fluid and blood plasma of marginally nourished Thai children before and after supplementation with a single, oral dose of 110 mg retinyl palmitate. After two months a significant rise of tear fluid retinol levels of the supplemented group was observed as compared to the non-supplemented group, while after four months no difference could be found. Determination of vitamin A levels in tear fluid may be useful in clinical eye research, with special regard to xerophthalmia.