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Purpose: To report a rare case of fungal keratitis caused by Plectosphaerella cucumerina ., Methods: This study retrospectively reviewed the medical records of a case of fungal keratitis., Results: Silt-lamp biomicroscopy revealed corneal infiltration and epithelial defects. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) were performed to assist in the diagnosis and evaluate corneal conditions. The isolate was identified as Plectosphaerella cucumerina by MALDI-TOF mass spectrometry. The patient was treated with topical 5% pimaricin and oral voriconazole for 1 month and recovered., Conclusion: Fungal keratitis caused by Plectosphaerella cucumerina is rare. AS-OCT and IVCM can help locate the lesion and diagnose fungal keratitis. Furthermore, MALDI-TOF mass spectrometry showed potential prospects in the identification of filamentous fungi. Plectosphaerella cucumerina rarely infects humans and is sensitive to antifungal agents such as pimaricin and voriconazole.

Purpose: To investigate the antioxidative effect and mechanism of pigment epithelium-derived factor (PEDF) on the ocular surface damage in diabetic mice., Methods: C57BL/6 mice were injected intraperitoneally with streptozocin to generate diabetic models and then 50 nM PEDF or artificial tears were used to treat the diabetic mice. Treatment was given three times a day for eight weeks. Corneal epithelial damage, corneal sensitivity, and tear volume were quantified by fluorescein staining, esthesiometer, and phenol red cotton thread, respectively. Animals were sacrificed at 16 weeks after diabetes and the whole globe specimens were subjected to histochemical staining. Reactive oxygen species (ROS) generation was detected by 2',7-dichlorodihydrofluorescein probe. The levels of receptor for advanced glycation end products (RAGE) and superoxide dismutase 1 (SOD1) were examined by quantitative real-time PCR and western blotting., Results: Topical application of PEDF improved corneal epithelial damage, increased corneal sensitivity, and tear volume in diabetic mice. ROS levels in the cornea were significantly higher in the diabetic mice than in the normal mice. Moreover, PEDF attenuated the accumulation of ROS, decreased the expression of RAGE, and elevated SOD1 expression in the cornea., Conclusions: Topical application of PEDF can alleviate diabetes-related ocular surface damage and increase tear volume, along with the improvement of oxidative stress status.

Purpose : To investigate the sterility of autologous serum eye drops used for ocular surface diseases. Methods : A total of 100 patients were enrolled. The serum was prepared as follows: 20% serum (20% S), 20% serum with dexamethasone (0.02 mg/ml) (20% S + Dex), and 20% serum with levofloxacin (0.1 mg/ml) (20% S + Lev). Serum samples were collected for normal microbial cultivation at 1, 3, 5, 7, 10, 14, 21, and 28 days. The last samples were also assessed on the 28th day by airtight microbial cultivation. Results : A total of 2400 samples were cultured, and the bacterial contamination rates of 20% S, 20% S+ Dex, and 20% S + Lev group were 4.75%, 3.38%, and 0.88%, respectively, for normal microbial cultivation. There was no significant difference in bacterial contamination among the three groups with times ( P = .502). Bacterial contamination of the 20% S + Lev group showed a significant difference in comparison with the 20% S or 20% S + Dex group ( P < .05) in two culture methods; however, no significant difference was found between the 20% S and 20% S + Dex group ( P = .208). There were two samples positive for fungi in the 20% S and 20% S + Dex group and three samples in the 20% S + Lev group in normal cultivation during 28 days. None of the samples was positive with fungi in airtight cultivation on the 28th day. There was also less bacterial contamination in airtight cultivation than in normal cultivation for the three groups on the 28th day. Conclusions : Our study shows that 20% autologous serum drops can be safely prepared and stored at 4°C in an open system under a strict protocol for at least 28 days, and antimicrobial agents could reduce the risk of contamination.

Purpose : To investigate the therapeutic efficacy of tumor necrosis factor (TNF)-α stimulated gene/protein 6 (TSG-6) in a rat model of corneal alkali injury. Methods : Corneal alkali injury was produced by placing an NaOH-soaked filter paper disk on the central cornea of the right eye of an anesthetized male Lewis (LEW/Crl) rat. Recombinant human TSG-6, or an equal volume of phosphate-buffered saline (PBS), was administered intravenously (IV), by anterior chamber (AC) injection, or as a topical drop. The affected eyes were photographed daily using a dissecting microscope and documented for clinical time course analysis of corneal opacification. Corneal tissue was excised at pre-determined therapeutic endpoints, with subsequent qRT-PCR or histological analyses. Results : The continuous monitoring of corneal alkali injury progression revealed TSG-6 treatments do not show sufficient effectiveness in vivo regardless of IV injection, AC injection, or topical application. Corneal opacification and neovascularization were not diminished, and gene expression was not impacted by these treatments. However, both IV and AC administration of TSG-6 significantly suppressed pro-inflammatory cytokines compared to PBS-treated eyes. Conclusion : We conclude that the therapeutic potential of TSG-6 is insufficient in a rat corneal alkali injury model.

Purpose: To examine if current development on using contact lenses for drug delivery of cysteamine to treat ocular symptoms of cystinosis can be tinted to mitigate photophobia common in patients by reducing transmittance Methods: Commercial contact lenses were placed in a carbon black solution to examine loading after lens synthesis. Silicone hydrogel contact lenses were also synthesized with carbon black added prior to UV curing. Transmittance was measured using UV-vis spectrophotometry over the range of 190-1190 nm and compared to unmodified contact lenses. Lens parameters of refractive index, ion permeability, and Young's modulus were measured using a refractometer, release of sodium chloride, and the cantilever method. Cysteamine release was measured by loading lenses into 5% cysteamine solution and then monitoring the release of the drug using UV-vis spectrophotometry. Vitamin E diffusion barriers were also added to lenses via ethanol solution, and the release of cysteamine from these modified lenses was also examined., Results: No leeching of carbon black was detected during experiments. Loading of pre-made contact lenses led to uneven distribution of carbon black throughout lens. Adding 0.3% carbon black to lens monomer solution prior to UV-curing led to even distribution and a transmittance reduction of approximately 50%. Ion permeability was reduced from 6.19 ± 0.90 x 10 -3 to 1.28 ± 0.06 x 10 -3  mm 2 min -1 , and Young's modulus was decreased from 1.58 ± 0.08 to 1.29 ± 0.06 MPa. Cysteamine releases from carbon black lenses with and without vitamin E were comparable to controls, although the loading solution of vitamin E/ethanol had to be tripled to achieve a similar mass loading to control., Conclusions: Carbon black increases the softness of contact lenses, but a loading of 0.3% maintains lens parameters required for wear. The release of cysteamine is also possible with carbon black lenses, albeit requiring a higher loading concentration of vitamin E to achieve similar release times.

Purpose: To compare the efficiency and ocular side-effect profile of topical loteprednol applied to one eye and topical dexamethasone applied to the other eye in the early period on the same patient who has subepithelial infiltrates (SEI)., Methods: The patients who developed bilateral SEI following epidemic keratoconjunctivitis (EKC) were applied topical loteprednol on one eye (group 2) and topical dexamethasone on the other (group 1)., Results: Decrease in the symptoms was faster in the dexamethasone group, but this difference between the groups was not statistically significant (p = 0.073). Both groups were found to have substantial recurrence. However, the difference between the groups was not statistically significant (p = 0.131)., Conclusions: The study has found that in the treatment of SEI, which developed after EKC, statistically similar results can be obtained with loteprednol, which is known to have fewer adverse effects.

Purpose: Application of amniotic membrane-conditioned medium (AMM) eye drops is a potential treatment alternative for therapy-resistant corneal epithelial defects. Our purpose was to determine the concentration of growth factors epidermal growth factor (EGF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGFβ1), fibroblast growth factor basic (FGFb), and interleukins, IL-1β, IL-6, IL-8, in AMM following different preparation methods., Methods: Amniotic membranes of 10 placentas were prepared and thereafter stored at -80°C using the standard method of our LIONS Cornea Bank. Following defreezing, amniotic membrane pieces with a standard size were inserted in a 12-well plate either complete or cut in small pieces, and 2000 µl DMEM culture medium was added. EGF, NGF, VEGF, TGFβ1, FGFb, IL-1β, IL-6, and IL-8 concentrations in the culture medium were determined following 8, 48, and 96 hours, and 1, 2, 3, and 4 weeks of incubation using enzyme-linked immunosorbent assay (ELISA)., Results: Concentrations of NGF, VEGF, TGFβ1, and IL-1ß were beyond the detection limit at all time points. EGF concentrations were between 0.14 and 0.80 ng/g tissue, FGFb between 0.48 and 2.89 ng/g tissue, IL-6 between 0.11 and 1.41 ng/g tissue, and IL-8 between 0.32 and 6.18 ng/g tissue. A significant difference between both preparation methods was shown for the IL-6 concentration after 8 and 48 hours (p < 0.001; p = 0.01) and in IL-8 concentration after 8 and 96 hours and after 3 weeks (p = 0.02; p = 0.002; p = 0.027)., Conclusion: AMM containing EGF and FGFb, and IL-6 and IL-8 AMM is a potential nonsurgical treatment alternative of therapy-resistant corneal epithelial defects. However, the most effective preparation method and the optimal harvesting time point are yet to be determined.

Purpose: To compare central corneal thickness (CCT) and specular microscopic indices in active unilateral anterior uveitis with the same indices 1 week after the initiation of treatment., Methods: This study included 30 eyes with active unilateral idiopathic anterior uveitis. CCT and specular microscopic indices were compared before and after 1 week of the treatment with topical medications., Results: At the first visit, mean CCT was significantly greater in affected eyes (mean ± standard deviation: 514.0 ± 23.0) than in fellow eyes (493.2 ± 10.6) (p < 05). There was a significant decrease in CCT of the involved eye 1 week after start of treatment to 494.1 ± 23.1 μm (p < 05). No significant differences were observed in the specular microscopic indices between the affected and fellow eyes before treatment and 1 week after the treatment., Conclusion: We found that eyes with unilateral active anterior uveitis had increased CCT in comparison to their healthy fellow eyes without a change in the specular microscopic indices.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially blinding diseases that affect the skin and mucous membranes. Although the cutaneous manifestations tend to be self-limited and resolve without sequelae, the chronic ocular complications associated with SJS/TEN can persist despite local therapy. Poor understanding of the underlying pathophysiology and lack of a standardized clinical approach have resulted in a paucity of data in regards to suitable treatment options. Inflammatory cellular infiltration and elevated levels of ocular surface cytokines in the conjunctival specimens of affected patients give credence to an underlying immunogenic etiology. Furthermore, the presence of ongoing ocular surface inflammation and progressive conjunctival fibrosis in the absence of exogenous aggravating factors suggest a possible role for systemic immunomodulatory therapy (IMT). We review in detail the proposed immunogenesis underlying chronic ocular SJS/TEN and the possible utility of systemic IMT.

Purpose: To investigate the effect of surgical wide excision and amniotic membrane transplantation with adjuvant mitomycin C 0.04% eye drops on recurrent conjunctival-corneal intraepithelial neoplasia (CCIN)., Methods: The authors applied amniotic membrane transplantation after total surgical excision of a tumor to a patient with recurrent conjunctival-corneal intraepithelial neoplasia. The tumor co-existed as a conjunctival lesion and corneal opacity. After one week, the patient received mitomycin C 0.04% eye drops four times a day for one month to prevent recurrence. Ocular complications and recurrence were evaluated under slit lamp microscopy for one year., Results: Corneal epithelium completely healed within one week after the surgery. Both conjunctival and corneal lesions were completely regressed and no recurrence has been found with follow-up to 24 months., Conclusions: Surgical wide excision and amniotic membrane transplantation with adjuvant topical MMC would be an effective treatment modality for treatment of recurrent CCIN.

Purpose: This study was undertaken to evaluate the efficacy of co-treatment with suberoylanilide hydroxamic acid (SAHA) and mitomycin-C (MMC) on corneal fibrosis in an in-vivo model., Materials and Methods: We examined the effect of co-treatment with MMC and SAHA, a potent histone deacetylase inhibitor (HDACi), on the corneal fibrosis and haze produced in rats following photorefractive keratectomy (PRK). We further examined the toxicity of this co-treatment on human corneal epithelial (HCE) cells in-vitro., Results: The combination of MMC and SAHA efficiently suppressed corneal fibrosis and haze following PRK. At the doses tested, SAHA had no inhibitory effect on human corneal epithelial cell viability, whereas MMC-treated cells showed increased apoptotic changes in Western blot testing and a fluorescence-activated cell sorting system. Co-treatment with SAHA and a low-dose of MMC minimized corneal haze after PRK and produced a significantly lower level of cytotoxic effects than treatment with MMC alone., Conclusions: Treatment with SAHA in combination with a low dose of MMC could be a novel and effective therapeutic strategy to suppress the proliferation of corneal myofibroblasts, thereby inhibiting corneal fibrosis or haze with minimal ocular surface toxicity.

Unlabelled: Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases., Materials and Methods: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation., Results: Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea., Conclusion: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.

Purpose: Using an in vitro cell culture model, bovine lactoferrin (BLF) stimulates healing of alkali-induced human corneal epithelial wounds. The present study examined the efficacy of BLF in promoting healing of corneal injury in vivo and explored BLF modulation of interleukin-1 (IL-1) during wound healing., Methods: Alkali injury was induced to BALB/c mice by exposure of the mouse cornea to a sodium hydroxide (NaOH)-soaked filter disc for 2 min. The corneal surface was irrigated after the injury with saline. Topical BLF in phosphate buffered saline (PBS) (10 µl, 62.5 μM), bovine serum albumin (BSA) (10 µl, 62.5 μM in PBS) or PBS only (10 µl) were applied three times daily to both the alkali-injured and uninjured eyes for 3 d. Wound healing was assessed using 0.1% fluorescein staining under slit lamp microscope. The corneas at 6 h, 24 h or 3 d post-injury and treatment were excised and examined histologically, homogenized corneal tissue was evaluated for expression of IL-1α and IL-1β., Results: After 6 h post-wounding and treatment no significant reduction of wound area was observed between treatments and infiltrating cells or IL-1 expression were not elevated in any group. By 24 h, BLF-treatment resulted in accelerated wound closure (100%) compared to PBS and BSA treatment (70% and 65%, respectively). BLF treatment reduced infiltrating cells compared to controls and no elevation of IL-1, whereas controls displayed elevated infiltrating cells and increased levels of IL-1. After 3 d, mice treated with BLF exhibited complete wound closure while control corneas still exhibited some minor defects. Resolution of inflammation with minimal remaining infiltrating cells was observed in all corneas by day 3, coincident to normal levels of IL-1α and IL-1β., Conclusion: BLF accelerated healing of corneal alkali injury in BALB/c mice which was associated with suppression of IL-1 and reduced infiltrating cells.

A 26-year-old female with "Progeria-like" phenotype presented with bilateral lagophthalmos and exposure keratopathy. Given the paucity of available skin to harvest, in conjunction with co-morbidities, standard surgery in the form of conventional skin grafting was contraindicated. We highlight the role of dermal fillers in such situations to reduce upper lid sulcus hollowing and increase weight of the upper lid in order to reduce lagophthalmos.

Objectives: To report the ocular complications associated with corneal wasp sting and to highlight the importance of eye protection in case of wasp offense., Methods: This was a retrospective, observational chart review., Results: A 34-year-old man was referred for severely decreased vision after being stung by a swap to the left cornea. Ophthalmologic examination showed a large corneal epithelial defect, anterior uveitis, and a left relative afferent pupillary defect. Vision was light perception. After treatment with cycloplegic, topical antibiotic, and systemic steroids for 2 weeks, the epithelial defect healed and anterior uveitis subsided; however, bulbous keratopathy and traumatic cataract developed. The visual acuity remained light perception with poor light projections. Twenty additional cases of corneal hymenoptera sting were reviewed from the English language literature, which shared certain characteristics including anterior uveitis, intractable glaucoma, traumatic cataract, toxic optic neuropathy, corneal scarring, and a catastrophic prognosis., Conclusions: Wasp stings of the cornea may bring disastrous ocular damages. Outdoor works should manage to protect your eyes when confronted with a hymenoptera attack.

Purpose: To conduct a pilot study of pegylated interferon alpha 2b (PEGIFNalpha2b) for treatment of ocular surface squamous neoplasia (OSSN)., Methods: Three patients with histologically proven OSSN were studied prospectively. Patients were given subconjunctival/perilesional injections of 1 microg/kg of PEGIFNalpha2b (PEG Intron, Schering-Plough, Kenilworth, NJ) until the tumor resolved. Patients were followed clinically and photographically for evidence of tumor resolution and recurrence., Results: All patients had clinical resolution of the tumor. The mean time to resolution was 47 days. During the follow-up time after resolution of the lesion (mean 41 months), one patient had disease recurrence 7 months after clinical resolution. This was successfully treated with one further injection., Conclusion: PEGIFNalpha2b may be a viable medical alternative for the treatment of OSSN. Future studies will be needed to evaluate whether PEGIFNalpha2b is as effective as recombinant interferon alpha 2b.

Purpose: To investigate ability of vitamin A (VA, retinol palmitate) to promote wound healing after injury in rabbit eye., Methods: After keratoconjunctival injury by 20 microL of n-heptanol, VA eye drops at 500, 1000, or 1500 IU/mL were started 6 times a day for 11 days. Fluorescein and rose bengal staining and histological analysis were performed., Results: Fluorescein staining was significantly reduced by 1000 and 1500 IU/mL of VA and rose bengal staining by all concentrations. Histological examination revealed acceleration of wound healing after 7 days (1500 IU/mL)., Conclusions: VA may be useful in treatment of keratoconjunctival injury.

We review the use of three topical medications for the therapy of ocular surface tumors: mitomycin C, 5-fluorouracil, and interferon alpha-2B. One hundred sixty patients with histologically or cytologically proven epithelial and melanocytic tumors were identified in the literature. Side effects occurred most often with mitomycin C, followed by 5-fluorouracil, and interferon alpha-2B. Patients most frequently experienced transient keratitis, redness, and irritation. Topical agents were used as both primary and adjuvant therapy. Rates of tumor regression for CIN and squamous cell carcinoma ranged from 80 to 96%, and 70% of pigmented tumors regressed after an average follow-up of 27 months.

Keratomycoses have recently emerged as an important cause of ocular morbidity, especially in third-world countries. Available antifungal agents are limited in their efficacy, due to limited penetration into the cornea, the fungistatic nature and the development of drug resistance. Effective usage of the available drugs is hampered by the inefficiency of currently available antibiotic sensitivity tests for fungal organisms. There is also limited knowledge regarding the ideal combination(s) of antifungal agents, including issues of synergism and antagonism. Despite these problems, recent publications indicate encouraging outcomes in the treatment of a large series of fungal keratitis. Advances include better drug formulations, new agents and novel methods of drug delivery into the eye. As our ability to deal with advanced fungal keratitis remains limited, the importance of early diagnosis has been stressed and molecular biological techniques may play an important role in the future. This article summarises the important new advances in these areas in the past 2 years and provides guidelines for the management of these serious corneal infections.

Purpose: By using both in vivo and in vitro (organ-cultured) systems, the optimal concentrations of hEGF to enhance epithelial healing after alkali wounds were evaluated in the rabbit cornea., Methods: Alkali-injured corneas (pi = 5.5 mm, 1 N NaOH, 60 s) were treated with 0.01, 0.1, 1.0, 10 and 100 ng/ml hEGF for the in vitro study. The healing of epithelium and endothelium was determined at 1, 2, 3, 4, and 6 days after treatment. For the in vivo experiment, the eyes were treated with 2, 5, 10, and 50 microg/ml hEGF 3 times per day. The measurement of epithelial healing rate, transmission electron microscopy and immunohistochemical observation were performed after 7 days treatment., Results: In in vitro tests, hEGF enhanced the epithelial healing rates, showing a maximum enhancement at the concentration of 1.0 ng/ml, and endothelial healing was increased at 100 ng/ml. In in vivo studies, no significant difference was observed in the rates of epithelial healing between control and each hEGF-treated group. Among the tested concentrations, 5 microg/ml hEGF induced the most active proliferation of basal cells and 50 microg/ml hEGF remarkably produced a vascular ingrowth to the central wound area. The thickness of re-surfaced epithelium was increased by hEGF in a concentration-dependent manner., Conclusions: The results of the present study indicate that a low concentration of hEGF may selectively enhance epithelial healing without affecting endothelial healing. The optimal concentration of hEGF for the stimulation of epithelial healing appears to be 5 microg/ml in rabbit corneal alkali wounds.

Purpose: After corneal injury, persistent epithelial defects (PED's) may occur due to the chronic failure of the regenerating epithelium to adhere to the underlying stroma. The aim of this study was to examine the potential of epsilonaminocaproic acid (EACA) as a topical treatment for PED's. EACA inhibits the activation of plasmin, which metabolizes fibronectin. Fibronectin, a glycoprotein, anchors corneal epithelium to the basement membrane and the underlying stroma., Methods: In anesthetized rabbits, PED's were induced with sodium hydroxide (1 N). Seven days later, during the late healing phase, treatment began with administration of EACA (30%) to the right eye and administration of vehicle alone to the left eye three times daily. A control group received neither EACA nor vehicle. Rabbits were treated for 19 days. PED's were visualized by fluorescein staining. Their size was mapped using digital planimetry., Results: After 11 days of treatment with EACA, treated PED's were 50% smaller than in corneas treated with vehicle alone. Following treatment for 15 days, corneas treated with EACA had significantly greater re-epithelialization than vehicle-treated or control corneas. Frozen sections stained immunofluorescently for fibronectin appeared to qualitatively contain more adherent fibronectin in treated corneas. Transmission and scanning electron microscopy indicated that the epithelium was more polymorphic, thinner and vacuolated in untreated controls compared to EACA treated eyes. Light microscopy demonstrated more continuous adherent epithelium after EACA treatment., Conclusions: Topically administered EACA decreases both the severity and incidence of persistent epithelial defects produced by alkali bums to the cornea. EACA appears to promote adherence of the regenerating epithelium to the underlying stroma. Thus, topically administered EACA may be an effective treatment for this chronic condition.

The study of experimental fungal infections requires effective animal models. Two such models in the rabbit model have been developed and applied to various aspects of topical antifungal therapy. In these models, the polyenes, as a class, are superior in efficacy to the imidazoles and flucytosine, but efficacy is clearly strain related. Corticosteroids, when administered concomitantly with antifungal agents, adversely influence antifungal activity in vivo. This steroid effect is inversely proportional to the efficacy of the antifungal agent. The corneal epithelium appears to be a significant barrier to the penetration of the polyene antibiotics. Although the predictive power of in vitro susceptibility testing as a guide to in vivo efficacy is uncertain, a correlation was seen between the in vivo and in vitro effect for amphotericin B against three strains of Candida albicans.

Isolated rabbit corneas bathed in Krebs-bicarbonate Ringer solution were observed for thickness changes after a 90 minute equilibration period. Control corneas swelled an average of 0.5 micron/hr, and placement of a polymethylmechacrylate (PMMA) contact lens on the epithelial surface caused the corneas to swell 24.5 microns/hr, an effect similar to 0.5 mM epithelial cyanide exposure. The pronounced swelling induced by PMMA lens placement was much less however, in the epithelial presence of 3.2 mM sodium oxalate (3.22 microns/hr) or 3.2 mM sodium oxamate (5.38 microns/hr). An equiosmotic excess of 4.8 mM NaCl was least active (15.89 microns/hr). On normal isolated corneas (without contact lenses), the Ringer containing an excess of 4.8 mM NaCl significantly deswelled the corneas (-13.44 microns/hr), which contrasted with oxalate and oxamate containing Ringer solutions (1.17 and 1.33 micron/hr respectively). The present study supports the notion that contact lens-induced edema results from stromal lactate accumulation, and suggests a potential alternative to osmotic therapy for its amelioration. These LDH inhibitors, in the concentrations used, have no acute osmotic or toxic effect on normal corneas in vitro.

Discrete 28mm2 epithelial lesions in paired rabbit corneas were treated four times daily with either vehicle alone or 10(-2)M or 10(-3)M Db cAMP in the presence or absence of either theophylline (10(-2)M) or epinephrine (5.5 x 10(-3)M). Cyclic GMP was also used either alone or with pilocarpine (1%). The lesion size was determined photographically at various intervals over 48 hours. No treatment regimen at the concentrations of cyclic nucleotides used had any influence on the rate of epithelial regrowth.

Several reports have appeared on the efficacy of topically applied 0.01% or 0.1% all-trans retinoic acid (0.04-0.4 millimolar) for treatment of xerophthalmia, conjunctival squamous metaplasia, and corneal epithelial erosions in humans and animals. An observation common to many of these studies is the occurrence of an adverse reaction to retinoic acid in the form of lid margin hyperemia and blepharoconjunctivitis. Since retinoic acid is biologically active at micromolar to nanomolar concentrations, it may be possible to reduce side effects while maintaining therapeutic effectiveness by reducing the retinoic acid concentration in ophthalmic formulations. In the present study, topical 0.005% retinoic acid in petrolatum ointment reversed corneal keratinization in xerophthalmic, vitamin A-deficient rabbits in 3-4 days while 0.0005% (2 micromolar) retinoic acid ointment was effective in 4-6 days. Further clinical trials of topical retinoic acid for treatment of ocular surface disease should be conducted using micromolar concentrations of retinoic acid which are expected to maintain a therapeutic effect while reducing adverse reactions.

Intrastromal injection with human serum albumin (HSA) in the rabbit cornea induced edema and a ring-shaped leukocyte infiltrate followed by neovascularization. The effect of topically administered lipoxygenase and cyclooxygenase inhibitors on this inflammatory keratitis was studied. The lipoxygenase inhibitors Bay 08276 and Rev 5901 and the cyclooxygenase inhibitor suprofen were given as 1% eye drops three times daily during the experiment. In eyes treated with lipoxygenase inhibitors leukocyte infiltration, neovascularization and edema formation decreased. In eyes treated with a cyclooxygenase inhibitor the period of neovascularization was slightly shortened and corneal edema decreased. No influence on leukocyte infiltration was seen.