Incidence of corneal infections after laser in situ keratomileusis and surface ablation when moxifloxacin and tobramycin are used as postoperative treatment.

PURPOSE: To assess the incidence, culture results, and visual outcomes of infectious keratitis after laser in situ keratomileusis (LASIK) and surface ablation when topical moxifloxacin was added to postoperative prophylaxis with tobramycin. SETTING: Clínica Baviera, Instituto Oftalmológico Europeo, Bilbao, Spain. DESIGN: Retrospective case series review. METHODS: The medical records of 55 255 patients (108 014 eyes) who had LASIK and surface ablation were reviewed to identify cases of infectious keratitis. The incidence, risk factors, clinical course, days to diagnosis, treatment, and final visual outcomes were recorded. These data were compared with previously published data of 221 437 eyes that received postoperative tobramycin alone. RESULTS: Post-LASIK infectious keratitis was diagnosed in 10 eyes (9 patients) and post-surface ablation infectious keratitis in 11 eyes (10 patients). The onset of infection was early in 40.00% of cases after LASIK and in 36.36% after surface ablation. Cultures were positive in 2 cases after surface ablation. Immediate flap lifting and irrigation with antibiotics were performed in all eyes after LASIK. The final corrected distance visual acuity was 20/20 or better in 7 cases after LASIK (70.00%) and 7 cases after surface ablation (63.64%) and 20/40 or better in all cases after LASIK or surface ablation. CONCLUSIONS: The incidence of infectious keratitis decreased from 0.025% to 0.011% (P < .001) per procedure after LASIK and from 0.200% to 0.066% (P < .001) after surface ablation. Infectious keratitis was less frequent after LASIK than after surface ablation. The frequency of infection, mainly early-onset infection, was lower when the postoperative treatment was tobramycin and moxifloxacin rather than tobramycin alone. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling changes.

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.

RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.

Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50µl, 5µg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases.

Recurrence of peripheral ulcerative keratitis on the corneoscleral button in a young man treated successfully with oral corticosteroids.

PURPOSE: To describe recurrent peripheral ulcerative keratitis (PUK) on the corneoscleral graft in a young man treated successfully with oral corticosteroids. METHODS: Interventional case report. RESULTS: A 21-year-old Malay man with no previous known medical illnesses presented with a sudden onset of peripheral corneal perforation. It was temporarily sealed with a multilayer amniotic membrane followed by patching with a corneoscleral button. One month later, a recurrence of PUK on the donor button was noted. It was successfully treated with oral corticosteroids. CONCLUSIONS: PUK without systemic manifestation may recur in the donor corneoscleral graft. Prompt intensive treatment with oral corticosteroids results in a favorable outcome.

L-arginine-threonine-arginine (RTR) tetramer peptide inhibits ulceration in the alkali-injured rabbit cornea.

PURPOSE: Proline-glycine-proline (PGP) peptides have been identified as inflammatory mediators initiating neutrophil invasion into alkali-injured cornea. The complementary peptide, arginine-threonine-arginine (RTR), has been shown to bind to the PGP sequence and impede neutrophil infiltration. A prior study showed that L-RTR tetramer and D-RTR tetramer, used alternately (14 times a day), resulted in significantly reduced incidences of corneal ulceration and severity. The purpose of this experiment is to determine the effectiveness of both tetramers, used separately, compared with control. METHODS: Rabbit corneas were exposed to 1 N NaOH for 35 seconds. Sixteen animals were randomly assigned to each of 3 groups: 1) phosphate-buffered saline (PBS), 2) 1.5 mM L-RTR, or 3) 800 microM D-RTR. One drop of each was administered hourly (14 times a day) for 36 days. Additional studies were done to assess neutrophil infiltration into corneas with and without RTR treatment. RESULTS: The severity of corneal ulceration in both RTR groups was statistically significantly different from the 21st day of the experiment to the end. As a result of ulcers healing in the L-RTR group, there was a statistically significant reduction in the number of ulcers beginning on day 22 versus control. Although there was healing in the D-RTR group, the incidence of ulcers was not significantly different from control or L-RTR. Morphometric analysis revealed decreased neutrophil (PMN) invasion with RTR treatment compared with PBS control. CONCLUSIONS: Binding of the PGP molecules by RTR tetramer seems to deprive the cornea of this neutrophilic chemotactic stimulus, leading to a reduction in the severity and incidence of corneal ulceration.

Corneal ulceration in south-east Asia III: prevention of fungal keratitis at the village level in south India using topical antibiotics.

AIM: To determine whether topical antifungal prophylaxis distributed by paid village health workers (VHWs) in south India is necessary after corneal abrasion to prevent fungal keratitis in a population where half of the ulcers are fungal. METHODS: Two panchayaths (village administrative units in Madurai district with a combined population of 48 039 were followed prospectively for 18 months by 15 VHWs who were trained to identify post-traumatic corneal abrasions. Patients fulfilling the eligibility criteria were randomised into two groups and treated with either 1% chloramphenicol and 1% clotrimazole ointment or 1% chloramphenicol and a placebo ointment three times a day for 3 days. Patients, doctors and VHWs were blinded to treatment. RESULTS: During the 18-month period, 1365 people reported to VHWs with ocular injuries, of whom 374 with corneal abrasions were eligible for treatment. Of these, 368 (98.5%) abrasions healed without complications. Two patients had mild localised allergic reactions to the ointment, two dropped out and two patients in the placebo group developed microscopic culture-negative corneal stromal infiltrates that healed in 1 week with natamycin drops. CONCLUSIONS: Both fungal and bacterial ulcers that occur after traumatic corneal abrasions seem to be effectively prevented in a village setting using only antibiotic prophylaxis.

Inhibitory effect of a complementary peptide on ulceration in the alkali-injured rabbit cornea.

PURPOSE: Two tripeptide chemoattractants, acetyl-proline-glycine-proline (Ac-PGP) and methyl-proline-glycine-proline (Me-PGP), are the primary triggers for early neutrophil invasion into the alkali-injured cornea. In the present study the effectiveness of a complementary peptide designed to inhibit the PGP chemoattractants (arginine-threonine-arginine [RTR] tetrameric peptide) and an apo A-1 mimicking peptide (5F) was investigated in the alkali-injured rabbit eye. METHODS: (L)-RTR tetramer, (D)-RTR tetramer, and 5F were tested in vitro for their effects on neutrophil polarization. Synthetic 5F was also tested in vitro for its effect on the neutrophil respiratory burst. In the alkali-injured rabbit eye model, the right corneas of 48 rabbits were exposed to 1 N NaOH for 35 seconds. Sixteen animals were randomly assigned to each of three groups: phosphate-buffered saline (PBS) control; 800 microM RTR (dextrorotatory) tetramer in PBS alternating each hour with 1.5 mM RTR (levorotatory) tetramer in PBS; and 12 microM 5F in PBS. One topical drop of each substance was administered hourly (14 times per day) for 33 days. The experiment was continued until day 42 with no additional drops administered. RESULTS: (L)-RTR tetramer and (D)-RTR tetramer inhibited neutrophil polarization activated by the PGP chemoattractants in vitro. Synthetic 5F did not inhibit neutrophil polarization in the presence of Ac-PGP or the respiratory burst of neutrophils in the presence of a metabolic stimulant derived from alkali-degraded corneas. During the entire animal experiment, statistically fewer ulcers occurred in the RTR tetramer group than in the PBS control group (43.8% vs. 87.5%, P = 0.0046). The frequency of ulceration in the 5F group (68.8%) was not significantly different from the PBS control group. CONCLUSIONS: The reduction in the frequency of corneal ulceration by the RTR tetramer possibly resulted from its complementary binding to Ac-PGP and Me-PGP in the cornea shortly after alkali injury, leading to a reduction in the early and late infiltration of neutrophils. RTR tetramer appears to hold enough promise to warrant additional study as a therapeutic drug for the alkali-injured eye.

The effectiveness of a topical antibiotic irrigating solution in a model of staphylococcal keratitis after lamellar keratectomy.

PURPOSE: To create a model of Staphylococcus aureus keratitis after lamellar keratectomy; to assess the toxicity of an antibiotic irrigating solution on the corneal stromal bed; and to test the chemotherapeutic effectiveness of a topical antibiotic, both alone and with an antibiotic-containing irrigating solution in preventing S. aureus keratitis after lamellar keratectomy. METHODS: The right eye of each of 38 rabbits were used in this study. In 18 eyes, a lamellar flap was created with a microkeratome, and an inoculum of S. aureus (either 1,000, 5,000, or 50,000 CFUs) was instilled under each flap; the eyes were examined for signs of infection and inflammation at 24 and 48 hours. In another five eyes, a lamellar flap was created in the same manner and the stromal bed was irrigated with 0.3% ofloxacin; the eyes were assessed for ocular inflammatory changes and evidence of crystalline deposits. Finally, in each of 15 additional eyes, 1,000 CFUs of S. aureus were instilled under a lamellar flap to create experimental infectious keratitis. The keratitis was treated according to three regimens: irrigation of the stromal bed with sterile balanced salt solution; irrigation of the stromal bed with 0.3% ofloxacin, followed by application of topical ofloxacin four times a day; application of topical ofloxacin only, four times a day. Eyes were examined for infection and ocular inflammatory changes at 24 and 48 hours. RESULTS: Staphylococcus aureus keratitis can consistently be produced under the stromal flap by inoculation of relatively few organisms. Irrigation of the stromal bed with commercial-strength topical ofloxacin does not appear to be toxic to the stromal bed, with no evidence of crystalline precipitates of the antibiotic. In our model of infectious keratitis after lamellar keratectomy, both topical ofloxacin alone and the combination of topical ofloxacin and irrigation of the stromal bed with 0.3% ofloxacin were effective at preventing S. aureus keratitis. However, the combined treatment of antibiotic irrigation plus topical antibiotic was more effective at preventing inflammation than topical ofloxacin alone. CONCLUSIONS: In this model of S. aureus keratitis after lamellar keratectomy, irrigation of the stromal bed with antibiotic plus topical antibiotic appears to be both safe and effective for preventing infection.

Xerophthalmia, keratomalacia and nutritional blindness.

Vitamin A deficiency remains a major cause of pediatric ocular morbidity. Over five million children develop xerophthalmia annually, a quarter million or more becoming blind. It is also a major pathway for measles-associated blindness, particularly in Africa. Treatment is practical and inexpensive, based upon the oral administration of 200,000 IU vitamin A on two successive days, at a cost of 10 cents U.S. Given the potential rapidity of corneal necrosis (keratomalacia) and the relative inaccessibility of health services to those at greatest risk, prevention is probably more important than treatment. Oral administration of high dose supplements (2000,000 IU every 3 to 6 months), vitamin A fortification of commonly consumed items, or best of all, increased dietary intake of natural sources of vitamin A will reduce the number of needlessly blind young children. Given recent evidence that vitamin A deficiency greatly increases overall mortality, even among children without evidence of xerophthalmia, the same prophylactic regimen may improve child survival by 35% or more.

Management of corneal foreign bodies.

Optimal management of corneal foreign-body injuries includes an accurate history, thorough examination of both eyes, atraumatic removal of the foreign body, elimination of the rust ring, appropriate antibiotic prophylaxis and protective patching. Pitfalls to be avoided include using topical steroids, which may promote ulceration from fungal contaminants, and prescribing topical anesthetics, which can mask the pain of a retained tarsal foreign body or a developing corneal ulcer. Careful records of care and follow-up are essential.