Keratoconus diagnosis with optical coherence tomography pachymetry mapping.

OBJECTIVE: To detect abnormal corneal thinning in keratoconus using pachymetry maps measured by high-speed anterior segment optical coherence tomography (OCT). DESIGN: Cross-sectional observational study. PARTICIPANTS: Thirty-seven keratoconic eyes from 21 subjects and 36 eyes from 18 normal subjects. METHODS: The OCT system operated at a 1.3 microm wavelength with a scan rate of 2000 axial scans per second. A pachymetry scan pattern (8 radials, 128 axial scans each; 10 mm diameter) centered at the corneal vertex was used to map the corneal thickness. The pachymetry map was divided into zones by octants and annular rings. Five pachymetric parameters were calculated from the region inside the 5 mm diameter: minimum, minimum-median, inferior-superior (I-S), inferotemporal-superonasal (IT-SN), and the vertical location of the thinnest cornea. The 1-percentile value of the normal group was used to define the diagnostic cutoff. Placido-ring-based corneal topography was obtained for comparison. MAIN OUTCOME MEASURES: The OCT pachymetric parameters and a quantitative topographic keratoconus index (keratometry, I-S, astigmatism, and skew percentage [KISA%]) were used for keratoconus diagnosis. Diagnostic performance was assessed by the area under the receiver operating characteristic (AROC) curve. RESULTS: Keratoconic corneas were thinner. The pachymetric minimum averaged 452.6+/-60.9 microm in keratoconic eyes versus 546+/-23.7 microm in normal eyes. The 1-percentile cutoff was 491.6 microm. The thinnest location was inferiorly displaced in keratoconus (-805+/-749 microm vs -118+/-260 microm; cutoff, -716 microm). The thinning was focal (minimum-median: -95.2+/-41.1 microm vs -45+/-7.7 microm; cutoff, -62.6 microm). Keratoconic maps were more asymmetric (I-S, -44.8+/-28.7 microm vs -9.9+/-9.3 microm; cutoff, -31.3 microm; and IT-SN, -63+/-35.7 microm vs -22+/-11.4 microm; cutoff, -48.2 microm). Keratoconic eyes had a higher KISA% index (2641+/-5024 vs 21+/-19). All differences were statistically significant (t test, P<0.0001). Applying the diagnostic criteria of any 1 OCT pachymetric parameter below the keratoconus cutoff yielded an AROC of 0.99, which was marginally better (P = .09) than the KISA% topographic index (AROC, 0.91). CONCLUSIONS: Optical coherence tomography pachymetry maps accurately detected the characteristic abnormal corneal thinning in keratoconic eyes. This method was at least as sensitive and specific as the topographic KISA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Amantadine-associated corneal edema potentially irreversible even after cessation of the medication.

PURPOSE: To describe the clinical features of 3 patients with amantadine-associated corneal edema, including the histopathologic findings from 1 patient who underwent corneal transplantation for irreversible corneal edema. DESIGN: Interventional case series. PARTICIPANTS: Three patients who sought treatment at the authors' institution with abrupt-onset, bilateral, diffuse corneal edema associated with systemic amantadine use. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Visual acuity, corneal thickness, slit-lamp observations, and histopathologic findings. RESULTS: The duration of use of amantadine ranged from 2 months to 6 years before onset of corneal edema. Discontinuation of amantadine resulted in resolution of corneal edema in both eyes of 2 patients. A third patient underwent a full-thickness corneal transplantation, and subsequently, edema developed in the grafted cornea. Cessation of amantadine therapy in this patient resulted in resolution of corneal edema in both eyes, but the ungrafted corneal eventually decompensated and became edematous, requiring corneal transplantation. Histopathologic analysis of the cornea buttons showed significant loss of endothelial cells. CONCLUSIONS: Amantadine can cause corneal edema that begins a few months to several years after institution of therapy, and the edema can occur even in a corneal graft. Prolonged corneal edema in the setting of amantadine use can be irreversible. In cases of corneal edema without an obvious causative disease, the systemic medication list of the patient must be reviewed, and amantadine must be considered as a possible cause.

Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates.

PURPOSE: Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN: Laboratory investigation. METHODS: Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS: MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. CONCLUSIONS: The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.

Multivariate model of refractive shift in Descemet-stripping automated endothelial keratoplasty.

PURPOSE: To relate in situ graft shape in Descemet-stripping automated endothelial keratoplasty (DSAEK) to surgically induced refractive error. SETTING: Academic eye institute. METHODS: High frequency arc-scanning ultrasound was performed in 7 patients enrolled in a prospective study of microkeratome-assisted endothelial keratoplasty approved by the Investigative Review Board. A region of interest spanning the horizontal meridian was defined for analysis of epithelial, host, graft, and total corneal thicknesses. Graft thickness profiles were fit by quadratic polynomials where the 2nd-order coefficients represent the posterior corneal curvature contributed by the graft. The curvature coefficient and central graft thickness were analyzed as predictors of induced refractive error. RESULTS: At final follow-up (mean 5.9 months +/- 3.2 [SD]), 3 patients had a hyperopic shift (+2.50 diopters [D] each), 3 had insignificant (< 0.50 D) refractive shifts, and 1 had a myopic shift. In the group with hyperopic shift, a negative lens effect was predicted by positive curvature coefficients, representing grafts that were thinner centrally than peripherally (mean +22.72 microm/mm(2); range +4.95 to +45.17 microm/mm(2)). In the group with minimal refractive shift, coefficients were less positive (mean +7.28 microm/mm(2); range +2.01 to +13.82 microm/mm(2)). The patient with a myopic shift (-1.00 D) had the only negative curvature coefficient (-0.64 microm/mm(2)). In a 2-predictor model of refractive shift, central graft thickness and the curvature coefficient together accounted for 86% of the variance in the refractive response to DSAEK (P = .025). CONCLUSION: Nonuniform thickness profiles and variable central graft thicknesses both contribute to refractive shift after DSAEK.

Late repeat Descemet-stripping automated endothelial keratoplasty.

PURPOSE: To report the outcomes of 2 patients who underwent repeat Descemet-stripping automated endothelial keratoplasty (DSAEK) 13 and 23 months after their primary surgeries. METHODS: Two patients underwent repeat DSAEK for late graft failure at approximately 1 and 2 years, respectively. The operative procedure involved removing the failed graft and replacing it with new donor tissue. RESULTS: The postoperative visual recovery was similar to the visual outcomes of primary DSAEK surgery, with both patients achieving 20/30 or better best spectacle-corrected visual acuity within 3 months. There were no signs of interface scarring after surgical removal of the failed donor disc. CONCLUSIONS: Late repeat DSAEK can result in rapid visual recovery without interface scarring.

External refinement of the donor lenticule position during descemet's stripping and automated endothelial keratoplasty.

The authors describe a technique to facilitate the centration of the donor lenticule during Descemet's stripping and automated endothelial keratoplasty. The donor corneal lenticule is unfolded and grossly centered in the anterior chamber using a barbed 30-gauge needle on a 3-cc air syringe or a reverse Sinsky hook. Fine adjustments to center the lenticule can be achieved by applying external pressure to the cornea with a laser in-situ keratomileusis flap roller. This simple technique provides a mechanism for simultaneously removing interface fluid and allows the surgeon to center the donor corneal lenticule without further risk of direct mechanical trauma to the donor endothelium.

Narrow-strip conjunctival autograft for treatment of pterygium.

PURPOSE: To determine the efficacy of narrow-strip conjunctival autograft surgery in the treatment of pterygium. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Twenty-one consecutive interventions between 1994 and 2005 in 20 eyes of 18 patients for primary (n = 17 cases) or recurrent (n = 4 cases) pterygia. INTERVENTION: Surgical excision of the pterygium and conjunctival transplantation with a narrow-strip technique. In all cases, a 2-mm-wide autograft was secured adjacent and posterior to the limbus, leaving a 2- to 3-mm zone of bare sclera between the graft and the anterior margin of the conjunctival wound. All conjunctival margins were secured by suture to bare sclera. MAIN OUTCOME MEASURE: Recurrence of pterygium at 12 months. RESULTS: Mean follow-up after surgery was 41 months (median, 42; range, 4-132). At 1 year and all time points thereafter, 18 of 19 (94.7%) cases were free of recurrence. One patient was lost to follow-up at 4 months, and another died after 9 months of follow-up. The lone recurrence occurred inferiorly in an eye that had undergone an adjacent narrow-strip conjunctival transplantation 6 months previously for a recurrent temporal pterygium. The same patient remains recurrence-free 67 months after inferior pterygium excision and a second narrow-strip autograft surgery. CONCLUSION: Narrow-strip conjunctival autografting appears to be an effective surgical technique in preventing pterygium recurrence. Creating an intervening bare sclera area between the secured conjunctival graft and the anterior margin of the conjunctival wound may be important in preventing recurrence.

Anterior segment and external ocular disorders associated with human immunodeficiency virus disease.

The eye is a common site for complications of human immunodeficiency virus (HIV) infection. Although cytomegalovirus retinitis remains the most prevalent of the blinding ocular disorders that can occur in individuals with the acquired immunodeficiency syndrome (AIDS), several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae. Some of these entities, such as Kaposi sarcoma, were well described, but uncommon, before the HIV epidemic. Others, like microsporidial keratoconjunctivitis, have presentations that differ between affected individuals with HIV disease and those from the general population who are immunocompetent. The treatment of many of these diseases is challenging because of host immunodeficiency. Survival after the diagnosis of AIDS has increased among individuals with HIV disease because of more effective antiretroviral therapies and improved prophylaxis against, and treatment of, opportunistic infections. This longer survival may lead to an increased prevalence of anterior segment and external ocular disorders. In addition, the evaluation and management of disorders such as blepharitis and dry eye, which were previously overshadowed by more severe, blinding disorders, may demand increased attention, as the general health of this population improves. Not all individuals infected with HIV receive potent antiretroviral therapy, however, because of socioeconomic or other factors, and others will be intolerant of these drugs or experience drug failure. Ophthalmologists must, therefore, still be aware of the ocular findings that develop in the setting of severe immunosuppression. This article reviews the spectrum of HIV-associated anterior segment and external ocular disorders, with recommendations for their evaluation and management.

Reopening of previously closed macular holes after cataract extraction.

PURPOSE: To evaluate the frequency of reopening of macular holes after cataract extraction. DESIGN: Retrospective, comparative, consecutive case series. METHODS: Two hundred and eleven eyes with idiopathic macular holes closed by vitrectomy were divided into four groups: Group 1: prior cataract extraction; Group 2: vitrectomy then cataract extraction; Group 3: vitrectomy only; and Group 4: vitrectomy and cataract extraction as a combined procedure. The main outcome measure of macular hole reopening was evaluated in relationship to multiple variables. RESULTS: Two hundred and eleven eyes were included: Group 1: 56 eyes; Group 2: 86 eyes; Group 3: 41 eyes; and Group 4: 28 eyes. Twenty-four macular holes reopened (11%) (mean follow-up 26.6 months, range, three to 118 months). The greatest number of macular hole reopenings, 17 (20%), were in Group 2. Cox multivariate analysis failed to demonstrate an association between duration of hole, serum use, internal limiting membrane peeling, or stage and reopening of a macular hole. Cox analysis showed a four-fold increased risk of reopening in Group 2 eyes (95% confidence interval [CI]: 1.7 to 11.2; P = .002). Eyes with cystoid macular edema after cataract extraction had a seven-fold increased risk of macular hole reopening (7.72; 95% CI: 2.79 to 21.3; P < .0005). Kaplan-Meier analysis showed increased rates of macular hole reopening in Group 2 eyes compared to the other 3 groups combined (log-rank P < .00005). CONCLUSIONS: Cataract extraction after successful vitrectomy for macular hole, when complicated by cystoid macular edema (CME), may increase the risk of macular hole reopening.

Use of an air-fluid exchange system to promote graft adhesion during Descemet's stripping automated endothelial keratoplasty.

Dislocation of the graft is a well-recognized complication of Descemet's stripping automated endothelial keratoplasty (DSAEK). We describe a technique to promote adhesion of the graft during DSAEK using an anterior chamber air-fluid infusion and exchange for direct control of the pressure and medium used to tamponade the graft against the host stroma.

Simple technique to unfold the donor corneal lenticule during Descemet's stripping and automated endothelial keratoplasty.

We describe a technique to facilitate unfolding and prevent inversion of the donor corneal lenticule during Descemet's stripping and automated endothelial keratoplasty (DSAEK). The donor corneal lenticule is unfolded in the anterior chamber using a bent 30-gauge needle on a 3 cc air syringe. The needle tip is used to pinion the edge of the lenticule while an air bubble is simultaneously injected between the folded edges of the donor graft. A gentian-violet dye mark placed on the peripheral stromal surface of the donor lenticule is used to confirm proper graft orientation. The simple technique of simultaneously fixating the donor lenticule while injecting air ensures that the graft unfolds correctly and minimizes potential mechanical trauma to the endothelium.

Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK).

PURPOSE: To evaluate visual acuity, refractive outcomes, and endothelial cell density 6 months after Descemet stripping and automated endothelial keratoplasty (DSAEK). METHODS: We performed an institutional review board-approved prospective study of a surgical case series of 34 patients at 2 institutions undergoing DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or aphakic bullous keratopathy with or without simultaneous phacoemulsification and intraocular lens implantation. Clinical outcomes, including best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and refractive astigmatism and topographic or keratometric astigmatism, were assessed at the 6-month postoperative examination and compared with preoperative values with paired Student t tests. The change in endothelial cell density from the eye bank examination to 6 months after transplantation was similarly evaluated. RESULTS: BSCVA averaged 20/99 preoperatively and 20/42 postoperatively (P < 0.0001). After DSAEK, 30 (88.2%) of 34 patients showed improved BSCVA, and 21 (61.8%) of the 34 patients achieved a BSCVA of 20/40 or better. For patients not undergoing simultaneous phacoemulsification and intraocular lens implantation, a hyperopic shift in refraction of 1.19 +/- 1.32 D was noted. Refractive astigmatism, topographic astigmatism, and keratometry showed no statistically significant change. Endothelial cell density of donor corneas averaged 2826 +/- 370 cells/mm, whereas the mean postoperative density was 1396 +/- 440 cells/mm. This finding corresponded to an average loss of 1426 cells/mm (50% loss; P = 0.0001). The first half of cases experienced an average cell loss of 1674 cells/mm (59% loss) compared with 1181 (41% loss) in the second half of cases (P = 0.005). Three (9%) of 34 grafts experienced iatrogenic graft failure and required reoperation with new donor tissue. Also, 9 (27%) of 34 grafts experienced dislocation in the early postoperative period and required repositioning. CONCLUSIONS: In this prospective study of DSAEK for bullous keratopathy and Fuchs endothelial corneal dystrophy, improvement of visual acuity was achieved with only a mild tendency toward hyperopic shift and without significant induced astigmatism. Endothelial cell loss was significant, however, and may be related to surgical experience.

Dysfunctional tear syndrome: a Delphi approach to treatment recommendations.

PURPOSE: To develop current treatment recommendations for dry eye disease from consensus of expert advice. METHODS: Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. RESULTS: A new term for dry eye disease was proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. CONCLUSION: Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.

A combined technique for surgical repair of Descemet's membrane detachments.

BACKGROUND AND OBJECTIVE: Descemet's membrane detachments are an uncommon complication after cataract surgery that can result in severe visual loss. A combined technique of intracameral gas injection and transcorneal suturing for the repair of Descemet's membrane detachments is described. PATIENTS AND METHODS: In this interventional case series, four cases of Descemet's membrane detachments with associated corneal edema observed following cataract surgery were successfully repaired using a combined technique of intracameral gas injection and transcorneal suturing. RESULTS: In all cases, Descemet's membranes were successfully reattached using the aforementioned technique. In three cases, the associated corneal edema resolved postoperatively. In the fourth case, the patient required a penetrating keratoplasty for persistent corneal edema despite immediate anatomical success following reattachment. CONCLUSIONS: Combined intracameral gas and transcorneal suturing appears to be an effective technique in the repair of Descemet's membrane detachments. Early intervention may prevent persistent or recurrent corneal edema.

A device to facilitate limbal stem cell procurement from eye bank donor tissue for keratolimbal allograft procedures.

PURPOSE: To develop a device that facilitates the procurement of corneal limbal stem cell grafts for keratolimbal allograft procedures used in the treatment of ocular surface disease associated with stem cell deficiency. DESIGN: Description of device design and technique for use. METHODS: The device is composed of a pedestal with a convex surface mounted to a flat platform. A corneoscleral button placed endothelial side down and centrally upon the convexity is secured by suction conveyed through a hollowed core in the pedestal that connects to fenestrated openings on the convex surface. A donut-shaped stainless steel ring placed on tension by springs braces the peripheral tissue. A circular corneal incision is created of a desired thickness by a suction trephine, and a crescent blade is utilized to peripherally dissect a donut-shaped keratolimbal allograft. RESULTS: This device facilitated the harvesting of the keratolimbal allograft tissue from four eye bank donor practice corneoscleral buttons and was then used to successfully procure grafts from six corneoscleral buttons used in three keratolimbal allograft procedures in three patients, one each with aniridia, alkali burn, and drug-induced limbal stem cell deficiency. CONCLUSIONS: The described device effectively facilitates procurement of corneoscleral buttons for keratolimbal allograft procedures. It appears to offer advantages over freehanded techniques and previously described devices used for the same purpose.

Surgical management of conjunctival lymphangiectasis by conjunctival resection.

PURPOSE: To report the treatment of symptomatic conjunctival lymphangiectasis with conjunctival resection. DESIGN: Interventional case series. METHODS: Retrospective review of three cases of patients with symptomatic unilateral conjunctival lymphangiectasis who had conjunctival resection of the involved tissue down to bare sclera. RESULTS: The surgical area reepithelialized without recurrence of the lymphatics. In all cases the patients have remained asymptomatic for at least 14 months. CONCLUSION: Conjunctival resection for symptomatic lymphangiectasis can be a successful therapeutic option for this condition.

Lymphedema-distichiasis syndrome and FOXC2 gene mutation.

PURPOSE: To describe the clinical characteristics of a family with autosomal dominant lymphedema-distichiasis syndrome and to report the results of analysis of the FOXC2 gene DESIGN: Observational and experimental study. METHODS: The setting was a clinical practice. The study population was 17 members of a family with lymphedema-distichiasis. Observation procedures were complete ophthalmologic examinations and collection of blood samples. DNA was extracted. Mutation analysis of the coding region of the FOXC2 gene was performed using direct sequencing of polymerase chain reaction (PCR) product and a restriction enzyme assay. The main outcome measure was inheritance of mutation in FOXC2 gene. RESULTS: Nine patients had distichiasis or lymphedema or both and eight did not. Sequencing of the coding region of the only translated exon of the FOXC2 gene revealed a C to A transversion at position 939 resulting in a Tyr313Stop codon with premature termination of translation and a truncated protein product. The mutation was present in all nine affected individuals and in an asymptomatic 9-year-old boy. CONCLUSIONS: Distichiasis-lymphedema syndrome results from mutations in FOXC2, a member of the forkhead/winged family of transcription factors. There is intrafamilial variation in the clinical expression of the mutation.

Chest computerized tomography in the evaluation of uveitis in elderly women.

PURPOSE: To describe the usefulness of chest computerized tomography (CT) in the evaluation of uveitis in elderly women and the clinical characteristics of patients with an abnormal chest CT scan. DESIGN: Prospective noncomparative case series. METHODS: We evaluated 30 elderly women, aged 61-83 years, with chronic iritis, vitritis, or choroiditis and with no definitive cause for their uveitis. All patients underwent a battery of diagnostic laboratory studies and chest CT. RESULTS: The diagnostic examination in most patients included serum angiotensin converting enzyme level, serum lysozyme, rapid plasma reagin level, fluorescent treponemal antibody-absorption test, purified protein derivative skin test, and chest x-rays. Chest CT performed on all patients showed parenchymal, mediastinal, and/or hilar adenopathy in 17 patients (57%). Histopathologic confirmation of sarcoidosis with noncaseating granulomas in the biopsy specimens was obtained in 14 patients: eight by mediastinoscopy, two by bronchoscopy, two by conjunctival biopsy, one by nasal biopsy, and one by vitreous biopsy. CONCLUSIONS: Chest CT can be useful in elderly female patients with chronic uveitis for identifying mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well as to help guide tissue confirmation and to rule out other diagnoses including lymphoma.

Nitric oxide generated by corneas in corneal storage media.

PURPOSE: The purpose of the study was to quantify nitric oxide release by human corneal buttons in storage media over time. METHODS: Group 1 consisted of six chambers of Optisol GS corneal storage media, each containing a viable human corneal button with an attached scleral rim (unsuitable for transplantation), sampled at 1-day intervals for at least 17 days (range, 17-28 days). Group 2 consisted of 34 chambers of Optisol GS media, each used to store a corneal button for penetrating keratoplasty, sampled immediately after each surgery. An unused vial of Optisol GS storage medium was sampled daily for 17 days to serve as a background medium control. The total amount of nitrite and nitrate in each sample was determined by a spectrophotometric method based on the Griess reaction. RESULTS: Data from the daily sampling in group 1 showed that nitrite and nitrate concentrations in storage media containing human corneas increase from a baseline level (beginning at the time the corneas are placed in the media) to an equilibrium concentration of 2.77 microM in a mean time of 6.15 days. Seventy-six percent of the data points from group 2 fell within the 80% predictive interval derived from group 1. No nitrite or nitrate was detected in background medium control samples. CONCLUSION: The progressive increase in nitrite and nitrate in corneal storage media over time suggests that nitric oxide is continuously released by corneas during storage before transplantation. Given the toxic free radical properties of nitric oxide, corneas in storage media may be subjected to the cumulative toxic effects of nitric oxide.