Dietary α-lipoic acid prevents UVB-induced corneal and conjunctival degeneration through multiple effects.

PURPOSE: This study investigated the effects of dietary α-lipoic acid (α-LA) against ultraviolet B (UVB)-induced corneal and conjunctival degeneration in a mouse model. METHODS: Female CBA mice were randomly divided into five study groups, including blank control, UVB without α-LA, and UVB with dietary α-LA at 1, 10, and 100 mg/kg body weight. Following UVB exposure, corneal surfaces were assessed along with immunohistochemistry for nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), malondialdehyde (MDA) accumulation, and P63⁺ basal cell distribution. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were determined by gelatin zymography. ELISA assay was performed to confirm the findings of immunohistochemistry for NF-κB, COX-2, and MDA, along with the levels of TNF-α and IL-6. Tear production and goblet cell density were determined after tear strip assay and periodic acid Schiff staining, respectively. RESULTS: The results showed that UVB irradiation caused corneal surface damage, polymorphonuclear leukocyte infiltration, and loss of P63⁺ basal cells. Dietary α-LA ameliorated the UVB-induced corneal damage while simultaneously reducing MDA accumulation and maintaining P63⁺ basal cell survival. NF-κB-p65, COX-2, TNF-α, IL-6, and MMP-9 activity were all reduced by dietary α-LA. In addition, α-LA helped to reverse aqueous tear reduction, conjunctival squamous epithelium metaplasia, and goblet cell loss after UVB exposure. CONCLUSIONS: Dietary α-LA can prevent UVB-induced corneal damage and can be used as a prophylactic agent prior to excessive UVB exposure.

Conjunctival proliferation after a mild pepper spray injury in a young child.

PURPOSE: To report a case of conjunctival proliferation in a 2.5-year-old boy after initial evidence of a mild chemical injury after ocular exposure to pepper spray (oleoresin capsicum). METHODS: Case report with ophthalmologic and histologic findings. RESULTS: A child presented with mild conjunctival injection and chemosis without any corneal erosion after direct exposure to pepper spray. Three weeks later, a significant conjunctival proliferation was found at the limbus, which was refractory to treatment with topical corticosteroids. Finally, proliferative tissue was surgically excised without clinical recurrence during 2 months of follow-up. CONCLUSIONS: We hypothesize that the young age of the patient may have been an important factor for the severe conjunctival proliferation in comparison to a mainly uncomplicated course of pepper spray injuries in most adults. We recommend the use of topical antiinflammatory treatment even in apparently mild pepper spray injuries, especially in young children.

The demonstration of changes in bulbar conjunctiva surface epithelium in the psoriatic patients treated with PUVA.

We investigated the effects of disease itself and PUVA treatment on surface epithelium of conjunctiva in psoriatic patients (PP) before PUVA and after PUVA therapy and in 32 healthy volunteers. Squamous metaplasia was detected in PP both before and after PUVA therapy. We concluded that PUVA treatment applied together with preventive measures, would lead to less severe ocular side effects.

[The effects of changes in phosphocalcic metabolism in ocular tissues in patients with chronic hemodialysis]. / Rasunetul tulburarilor metabolismului fosfocalcic asupra tesuturilor oculare la hemodializatii cronic.

Extraskeletal calcification is a common complication of chronic renal failure. It is well known that in dialysis patients the elevated calcium phosphate product is associated with the development of corneal and conjunctival calcification, but there is no association between the degree of the calcifications and the levels of calcium phosphate product. This paper is supposed to present briefly the main hypothesis who explain the mechanism that generates the deposition of the calcium salts to the anterior segment of the globe.

Epidemiología de las lesiones conjuntivales y su correlación clínico-patológica / Epidemiology of conjunctival lesions and clinical-pathological correlation

Se realizó una revisión de los 1166 casos de lesiones conjuntivales recibidos por el Laboratorio de Patología Ocular del Hospital Clínico de la Universidad de Chile entre los años 1968-2005. En base a ella se describen los distintos diagnósticos histopatológicos según su frecuencia, distribución por sexo, edad, localización y tiempo de evolución. La edad promedio para los casos fue de 36 años con un 51,5 por ciento de hombres afectados y un tiempo de evolución promedio de 68 meses. Las lesiones más frecuentes fueron las pigmentarias (44,2 por ciento), seguidas de las epiteliales (22,7 por ciento) y los cuadros infecciosos (10,9 por ciento). La localización más frecuente para todas las lesiones fue bulbar. Se estableció, además, una correlación entre los diagnósticos clínicos e histopatológicos, la cual resultó ser positiva en un 60,9 por ciento, siendo marcadamente superior para las lesiones pigmentarias e inferior para lesiones degenerativas, cuadros infecciosos y tumores clasificados como pre-malignos o malignos.

We made a retrospective review of 1166 cases of conjuntival lesions, accepted for its study at the Laboratory of Ocular Pathology, University of Chile, from 1968 to 2005. Based on this survey, different histopathologic diagnosis were described, characterized by its frequency, gender distribution, age, location and time of evolution. The average age was 36 years, with a 51,5 percent being male, and an average time of evolution of 68 months. Most frequent lesions were pigmented (44,2 percent), followed by epithelial (22, 7 percent), and infectious diseases (10,9 percent). The most frequent location was bulbar. A clinical - pathologic correlation was established, being positive in 60,9 percent of cases. It was noticeable superior for pigmented lesions, and inferior for degenerative lesions, infectious disease and tumors classified as pre malignants or malignants.

Disodium cromoglycate inhibits capsaicin-induced eosinophil infiltration of conjunctiva independent of mast cells.

PURPOSE: To investigate whether disodium cromoglycate (DSCG) inhibits capsaicin-induced eosinophil infiltration of the conjunctiva independent of mast cells. METHODS: We administered 5 microl of capsaicin solution (10(-5) M) into the conjunctival sacs of mast cell-deficient W/W(v) mice (12 animals) and wild-type mice (12 animals). As controls, the eyes of 12 wild-type and 12 W/W(v) mice were treated with phosphate-buffered saline. Following treatment, the eyelids and eyeballs were removed en bloc at 3, 9, or 24 h, and were histologically examined. The number of infiltrated eosinophils and the expression of vascular cell adhesion molecule-l (VCAM-1) in the conjunctiva were quantified by the staining method of Hansel and immunohistochemical analysis. We also investigated whether treatment by depletion of neuropeptides or by DSCG administration could suppress the capsaicin-induced eosinophil infiltration of the conjunctiva. RESULTS: In both W/W(v) and wild-type mice, eosinophil infiltration of conjunctival tissues was observed 3 h after capsaicin administration. In both strains of mice, the number of infiltrated eosinophils increased over time, with VCAM-1 expression on vascular endothelial cells peaking at 9 h after treatment, and decreasing gradually within 24 h after treatment. In both the neuropeptide-depleted and the DSCG-treated groups, eosinophil infiltration and VCAM-1 expression were suppressed in comparison with the nontreated group. CONCLUSION: DSCG can directly inhibit neuropeptide-induced eosinophil infiltration of the conjunctiva independent of mast cells.

SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a primary head-pain syndrome, which is often refractory to any medical treatment. Concerning the pathophysiology of SUNCT, hypothalamic involvement ipsilaterally to the pain has been suggested based on the clinical features and one functional imaging case report. Here we now report a new case with SUNCT and the concomitant cerebral activation pattern (fMRI) during the pain attacks. In addition to an activation of several brain structures known to be generally involved in pain processing, bilateral hypothalamic activation occurred during the pain attacks, arguing for a central origin of the headache. Interestingly, this patient became completely pain free after surgical decompression of the ipsilateral trigeminal nerve. We hypothesize that in this case with a central predisposition for trigeminal autonomic cephalgias, a peripheral trigger with ectopic excitation might have contributed to the clinical picture of SUNCT.

Conjunctival and tear film changes after vitamin C and E administration in non-insulin dependent diabetes mellitus.

BACKGROUND: The purpose of our research was to investigate the effect of supplementation with vitamin C and E on ocular surface cytology specimens and related parameters in diabetic patients. MATERIAL/METHODS: 60 patients were enrolled in the study. The patients were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) for 10 days. Conjunctival brush cytology specimens were obtained before and after treatment. Schirmer tests, break-up time and ocular ferning tests were also performed. RESULTS: Goblet cell densities were 50 cells/per field before and 59 cells/per field after supplementation (p=0.002). The stage of squamous metaplasia was 1.12+/-0.42 before and 0.88+/-0.41 after supplementation (p=0.011). The changes were accompanied with improved values for the Schirmer test (p<0.001), break up time (p=0.001), and ocular ferning (p<0.001). CONCLUSIONS: Diabetes mellitus is associated with increased oxidative stress. Our study suggests that supplementation with antioxidant vitamins C and E probably plays an important role in improving the ocular surface milieu.

Effect of gefarnate on the ocular surface in squirrel monkeys.

PURPOSE: To investigate the ability of gefarnate (geranyl farnesylacetate) to stimulate goblet cell function in the primate eye after a mild alkali injury of the tarsal conjunctiva. METHODS: A bilateral injury was created on the conjunctival surface of the lower eye lid of squirrel monkeys by means of a 30-second application of a 4-mm diameter piece of filter paper wetted with 0.5% NaOH. Gefarnate drops (1%) were administered to one eye of each monkey and vehicle alone in the contralateral eye six times a day, 5 days a week for 4 weeks. Slit-lamp biomicroscopy, impression cytology staining of the ocular surface, fluorescein and rose bengal staining, and Western blot for mucin were performed before injury and weekly thereafter. Light microscopy was used to evaluate the lower conjunctiva. RESULTS: Topical application of gefarnate was not associated with any adverse ocular surface effects. Goblet cell repopulation after injury was significantly greater in the gefarnate-treated eyes compared with the vehicle-treated eyes. In the gefarnate-treated eyes, tear mucin content was significantly greater at 1 week after injury. Fluorescein staining was significantly reduced at 3 weeks after injury, and rose bengal staining was significantly reduced in the area of the wound at 2 weeks in the gefarnate-treated eyes compared with the vehicle-treated eyes; at other times, conjunctival staining in the two groups of eyes was not significantly different. CONCLUSIONS: Gefarnate promotes goblet cell repopulation and increases mucin production after a conjunctival injury. No adverse affects of the treatment were found. Thus, this agent may be useful in conditions that diminish goblet cell function.

Suspected hypovitaminosis A in a colony of captive green anoles (Anolis carolinensis).

In a colony of 18 green anoles (Anolis carolinensis), 3 animals experienced focally thickened lips, ulcerative cheilitis, lethargy, depression, and weight loss over a 5-month period. In addition to crickets fed fresh fruit and leafy green vegetables, the diet of the green anoles consisted of a supply of mealworms that had been dusted with a commercial liquid vitamin supplement. The history, clinical findings, and histopathologic lesions were suggestive of hypovitaminosis A, which is known to cause squamous metaplasia of the mucus secreting glands and epithelial surfaces in many species.

Mitotic effect of autologous blood injection and diode laser bleb revision on rabbit filtration blebs.

OBJECTIVE: To investigate the effect of intrableb autologous blood injection and diode laser bleb revision on cellular proliferation in filtration blebs of rabbits. METHODS: Bilateral filtration surgery with mitomycin was performed on 19 white 2.5- to 3-kg New Zealand rabbits. Autologous blood injection (n = 9) or diode laser bleb revision (n = 10) was performed on blebs of right eyes (intervention eyes) on day 14 after filtration surgery. The blebs of the left eyes served as controls. Cellular proliferation was assessed by in vivo incorporation of 5-bromo-2'-deoxyuridine (BrdU), after BrdU, 10 mg/kg, was injected via the ear vein on days 15, 16, and 18. The rabbits were euthanized on day 21. Conjunctival sections were stained with hematoxylin-eosin for total cell counts and with anti-BrdU antibody for counts of proliferating cells. The BrdU labeling index was calculated by dividing the mean proliferating cell count by the mean total cell count. RESULTS: The BrdU labeling index was significantly increased in the blood-injected eyes as compared with the control eyes (P = .03). The BrdU labeling index was increased in the diode laser-revised eyes as compared with the control eyes, approaching significance (P = .06). Intraocular pressure increased significantly in the eyes that underwent bleb interventions in both groups from baseline and compared with the control eyes. CONCLUSIONS: Intrableb autologous blood injection and diode laser bleb revision stimulate cellular proliferation in the rabbit filtration bleb, which may contribute to the rise in intraocular pressure observed clinically after these interventions.

The role of serum calcium in the development of the acute red eye in chronic renal failure.

In patients with chronic renal failure treated by long-term dialysis, inflammatory reactions occasionally develop in the bulbar conjunctiva; the episcleral tissue is only rarely involved. Diffuse congestion of both the conjunctiva and episclera was present in 5.3% of our patients and was associated with a sudden, marked rise in serum calcium. Histopathological examination suggests that this form of hyperemia, clinically preceded by a marked shedding of calcific precipitates, is the result of a neurogenic-driven inflammatory reaction in which mast cell degranulation is mediated by the axon reflex. Focal hyperemia associated with elastosis ("pingueculitis") was present in 6.7% of the patients. This type of hyperemia was observed after an extended period of increasing levels of BUN and seemed independent of both serum calcium and phosphorus. Diffuse hyperemia of the conjunctiva, being clinically distinctly different from the combined diffuse conjunctival and episcleral hyperemia, was also observed in 6.7%. Diffuse conjunctival hyperemia seemed to be associated with low BUN. Here, again, there was no association with serum calcium and phosphorus levels.

Diffuse and focal hyperaemia of the outer eye in patients with chronic renal failure.

In 8 of 57 patients with chronic renal failure that all had deposition of calcium salts in the limboconjunctival area, a focal hyperaemia of the conjunctiva was observed. This focal hyperaemia developed gradually around one or more greyish, slightly elevated, areas situated in the bulbar conjunctiva in the interpalpebral fissure. Clinically these lesions are very much alike inflamed pingueculae. Three patients showed a diffuse inflammatory reaction of the eye that was characterized by a waxy red episcleral and conjunctival hyperaemia extending beyond the palpebral fissure. The average value of the serum calcium concentration in these patients was particularly high and statistically significantly higher than in patients with calcification but without inflammatory signs and also higher than in patients that showed focal hyperaemia. In addition to the focal hyperaemia and the diffuse hyperaemia, we observed another diffuse hyperaemia located principally in the conjunctival tissue. This conjunctival redness often followed the focal hyperaemia associated with pingueculae or preceded the more acute fiery red episcleral hyperaemia, but it could also be present in isolation.

Metastatic or dystrophic conjunctival calcification in renal failure?

In renal failure the incidence of pingueculae is significantly higher than in a comparable control group but there is no evidence that the calcific precipitation in renal failure is of a dystrophic nature. The lime salts are not located within the area of elastotic degeneration, a prerequisite for dystrophic degeneration. Moreover there is no association between the magnitude of the conjunctival degeneration and the degree of calcification. This makes it likely that the calcium precipitates represent metastatic calcification even though admittedly support for this assumption is tenuous.

Topical retinoic acid in dysplastic and metaplastic keratinization of corneoconjunctival epithelium.

We report four cases of corneoconjunctival keratinization that were successfully treated with topical retinoic acid ointment. In two cases keratinization was due to squamous metaplasia and in two others it was secondary to intraepithelial corneoconjunctival neoplasia. Treatment reversed severe keratinization in a case of drug-induced pseudopemphigoid and stabilized the disease in one of the two affected eyes without additional treatment. In a case of ocular cicatricial pemphigoid, retinoic acid was useful as an adjuvant therapy to immunosuppression, by reversing keratinization of the conjunctiva. In two cases of corneoconjunctival neoplasia, lesions regressed markedly. Long-term treatment was well tolerated in three patients. Our findings suggest that retinoic acid ointment is effective in treating severe squamous metaplasia in cicatrizing diseases of the conjunctiva. Our findings indicate further that retinoic acid seems to inhibit growth of corneoconjunctival neoplasias and thus might be useful complementary therapy in this situation.