Richard W. Yee

The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcommittee

Diagnostic tests of meibomian gland dysfunction (MGD) and of MGD-related disorders are based on the demonstration of abnormal anatomy and physiology of the glands and the detection of specific pathologic events. For this reason, this subcommittee report is divided into two sections. In part I, those aspects of meibomian anatomy and physiology that are relevant to currently available tests are described; a fuller account of the anatomy and physiology is provided in the report of the Anatomy Subcommittee of this workshop. In part II, each test and its performance is described in detail. In part III, the practical application of selected tests is summarized and recommendations for future approaches are made. Additional recommendations and a summary of pertinent literature and concepts are presented in Appendices 1 to 17.

Corneal Aberrations and Visual Performance After Radial Keratotomy

BACKGROUND Refractive surgery and videokeratography have allowed us to study the effects on visual performance of relatively large changes in corneal aberration structure induced by surgical changes in corneal shape. METHODS We quantified in one eye of nine normal and 23 radial keratotomy patients, the area under the log contrast sensitivity function (AULCSF) and corneal first surface wavefront variance for two artificial pupil sizes (3 and 7 mm). Contrast sensitivity was measured with sine-wave gratings at six spacial frequencies. Wavefront variance was derived from videokeratographs using Zernike polynomials. RESULTS For normals eyes there were no significant changes over time. For eyes that had radial keratotomy, there were significant pupil size-dependent changes. For the 3 mm pupil, there were significant surgery-induced changes in the corneal wavefront variance which became large (approximately 30 times preoperative values) at 7 mm. Significant correlated changes in AULCSF for the 7 mm pupil but not for the 3 mm pupil occurred immediately following surgery and remained. CONCLUSIONS Radial keratotomy, like photorefractive keratectomy, shifts the distribution of aberrations from third order dominance (coma-like aberrations) to fourth order dominance (spherical-like aberrations). Radial keratotomy-induced aberrations and loss in contrast sensitivity are reduced with increasing clear zone diameter. Radial keratotomy induces an increase in the optical aberrations of the eye and the increase for large pupils (7 mm) but not small (3 mm) is correlated to a decrease in contrast sensitivity.

Intraoperative mitomycin in primary pterygium excision: A prospective, randomized trial

PURPOSE Conjunctival autograft transplantation and postoperative mitomycin therapy are two adjuvant treatment methods shown to lessen the high pterygium recurrence rate seen with simple excision alone. The authors conducted a prospective, randomized study comparing these two techniques with a relatively new treatment method using intraoperative mitomycin application. METHODS Fifty patients with 56 primary pterygia were randomized to 1 of 3 treatment groups: conjunctival autograft (group 1), postoperative mitomycin 0.2 mg/ml four times a day x 7 days (group 2), and intraoperative mitomycin 0.4 mg/ml x 3 minutes (group 3). The mean follow-up time was 16 months (range, 6 to 28 months). RESULTS Recurrences developed in 4 (22.2%) of 18 eyes in group 1, 4 (21.1%) of 19 eyes in group 2, and 2 (10.5%) of 19 eyes in group 3. Complications developed in two, patients from group 2, scleral thinning managed successfully with a scleral patch graft, and epithelial toxicity that resolved on discontinuation of mitomycin on postoperative day 6. There were no complications in the other two groups. CONCLUSIONS Intraoperative mitomycin is a simple and effective alternative to postoperative mitomycin therapy, showing the lowest recurrence rate in their series with no toxicity during the study period. If the decision is made to use adjunctive mitomycin, the authors recommend intraoperative application over postoperative administration.

The effect of drop vehicle on the efficacy and side effects of topical glaucoma therapy: a review.

Purpose of review Topically applied medications are frequently used in ophthalmology to treat acute and chronic conditions, and are considered to be safer than their systemically applied counterparts, due to the reduced rate of systemic side effects. Recent findings Many experimental and clinical studies have reported that the long-term use of topical medications in chronic ophthalmic conditions, such as glaucoma, may adversely affect the ocular surface. Preservatives play a pivotal role in almost all multidose ophthalmic preparations, inhibiting microbial growth and preserving the active drug. Consequently, preservatives are partially responsible for ocular side effects, although the exact mechanism of these side effects is not known. Summary The role of preservatives in the efficacy and side effects of antiglaucoma drugs is reviewed. The recent advances in preservative technologies and their role in decreasing the side effects associated with antiglaucoma drugs are also discussed.

Comparison of the relative toxicity of travoprost 0.004% without benzalkonium chloride and latanoprost 0.005% in an immortalized human cornea epithelial cell culture system.

The purpose of this study was to compare the relative toxicity of a new topical ophthalmic glaucoma medication, travoprost 0.004% without benzalkonium chloride (BAK), with that of commercially available latanoprost 0.005% (preserved with 0.02% BAK) in immortalized human corneal epithelial cells (HCEs). Tissue culture plates (96 well) containing HCEs were divided into 6 groups. Two groups served as negative controls (70% methanol and gentamicin). Another 2 groups—1 in corneal epithelial culture media and the other in a hydroxypropyl (HP)-Guar gellable lubricant eyedrop—served as live controls. The travoprost 0.004% without BAK and latanoprost 0.005% groups were exposed to 100 μL of the undiluted solutions. Cells were incubated for 25 min at 37°C. A live/dead assay was used to measure the effects of travoprost without BAK and of latanoprost on HCEs compared to 70% methanol and culture medium. Between the 2 glaucoma medications tested, travoprost 0.004% preserved without BAK showed significantly less toxicity on HCEs than did latanoprost 0.005%. This difference may have ramifications in terms of tolerability for patients who use these topical glaucoma drugs on a long-term basis.

The use of topical cyclosporin A in ocular graft-versus-host-disease.

Ocular manifestations of GVHD include keratoconjunctivitis sicca, cicatricial lagophthalmos, sterile conjunctivitis, persistent corneal epithelial defects, corneal ulcers and corneal melting. Conventional initial therapy such as lubrication and topical steroids is directed to treat decreased tear production and ocular surface abnormalities. The purpose of this study was to illustrate the possible benefit of topical cyclosporin A 1% (CsA) as an adjunct in managing ocular surface abnormalities in five cases of GVHD refractory to conventional therapy. Five clinical case reports of chronic GVHD patients in whom conventional therapy was inadequate to stop the progression from its initial presentation are described. Patient presentation varied in severity on a spectrum of mild to moderate diffuse punctate epithelial erosions to sterile necrotizing corneal melts. Although systemic therapy for GVHD consisting of systemic immunosuppressants (ie cyclosporin A and corticosteroids) was given to these patients, this therapy was insufficient in managing the ocular manifestations of the disease. Topical CsA was added to the treatment regimen and the progression of the ocular disease was recorded. The addition of topical CsA 1% probably helped in controlling the epithelial keratitis and melting process in our reported cases and we conclude that topical CsA may be an appropriate modality in managing ocular surface abnormalities in patients with ocular GVHD after conventional treatments have been tried. However, a further randomized clinical prospective study is needed to evaluate the efficacy of topical CsA in managing these problems in GVHD patients.

Ocular Integrity after Refractive Procedures

PURPOSE The purpose of the study was to determine the integrity of human eyes after refractive procedures. METHODS Whole human globes underwent either radial keratotomy (RK) with eight incisions, automated lamellar keratoplasty (ALK), photorefractive keratectomy (PRK), or excimer laser assisted in situ keratomileusis (LASIK). Eyes then were subjected to quantitatively increasing levels of trauma until rupture occurred. RESULTS All eyes operated on required less energy to rupture as compared with that of control eyes. The mean number of trials required for rupture is as follows (energy doubled with each successive trial): normal, 4.29; LASIK, 3.80; ALK, 3.67; PRK, 3.60; and RK, 2.83. The level of energy required to rupture normal, ALK, PRK, and LASIK eyes was not significantly different. All RK eyes ruptured at incisions. Most ALK, PRK, and LASIK eyes ruptured near the flap edge or limbus. Most normal eyes ruptured with both corneal and scleral involvement. Age of tissue donors at the time of death and time elapsed between death and procedure were not significantly different between groups (P = 0.88 and 0.79, respectively). CONCLUSIONS The energy required to rupture ALK, PRK, and LASIK eyes is not significantly different from that for normal eyes. The RK eyes ruptured with significantly less energy than did normal eyes. All RK eyes ruptured at incision sites.

Laser epithelial keratomileusis for myopia with the autonomous laser

PURPOSE To describe the refractive outcome, objective clinical data, and subjective patient experiences after laser epithelial keratomileusis (LASEK) at 1, 3, and 6 months after surgery. METHODS This was a retrospective, nonrandomized, comparative study of 58 LASEK-treated eyes (36 patients) with myopia (with and without astigmatism) between -1.50 and -14.75 D (mean -7.80 +/- 2.90 D, median -7.90 D). Refractive surgery was performed using the Alcon Summit Autonomous LADAR Vision excimer laser. Manifest refraction, best-spectacle and uncorrected Snellen visual acuity, stability of refraction, and corneal haze were evaluated before surgery and up to 6 months after surgery. A group of randomly selected LASIK-treated eyes were compared at each time point. RESULTS Patients who opted for monovision (n=12) were excluded. In the emmetropia targeted eyes (n=46), 45%, 83%, 85%, and 89% achieved 20/40 or better uncorrected Snellen visual acuity (UCVA) at 1 day, 1 week, 2 weeks, and 1 month respectively. At 6 months, 73% (n=28) of eyes treated achieved UCVA 20/20 with 97% achieving 20/40 or better (mean, -0.51 D). At 3 and 6 months, 71% (n=46) and 68% (n=28) were within +/- 0.50 D of emmetropia. The percentage of eyes that achieved UCVA 20/40 or better at 6 months was 97% (n=28). Visually significant corneal haze was evident in two LASEK-treated patients (four eyes) at 6 months. No eyes lost two or more lines of best spectacle-corrected Snellen visual acuity. CONCLUSIONS Preliminary data suggest that LASEK appears to be a safe, effective, and comparable alternative to LASIK, even for higher amounts of myopia. A prospective, randomized clinical trial is needed to better define the role of LASEK as it compares to other refractive procedures, specifically LASIK and PRK.

Prediction of corneal haze using an ablation depth/corneal thickness ratio after laser epithelial keratomileusis

PURPOSE To investigate the usefulness of ablation depth/corneal thickness (AD/CT) ratio to predict corneal haze after laser epithelial keratomileusis (LASEK) using a retrospective, comparative, interventional case series. METHODS Fifty patients (90 eyes; mean age 40.9 years) with myopia, hyperopia, and/or astigmatism underwent bilateral or unilateral LASEK for correction of refractive error. After epithelial flaps were created using an 18% alcohol solution, bilateral or unilateral LASEK was performed using the Alcon Autonomous LADARVision 4000 excimer laser. Visual acuity (best spectacle-corrected and uncorrected) and refractive error were measured before and after LASEK. Corneas were assessed by two independent evaluators under a slit-lamp biomicroscope with broad tangential illumination. The relative haze scale was quantitated: 0 (clear), 0.5+ (trace), 1+ (mild), 2+ (moderate), 3+ (marked), and 4+ (severe). RESULTS Mean preoperative spherical equivalent refraction was -5.46 +/- 3.74 D (range -12.375 to +5.00 D), mean ablation depth was 93.04 +/- 45.03 microm (range 21.2 to 207.2 microm), and mean AD/CT ratio was 0.18 +/- 0.09 (range 0.04 to 0.41). Of 90 eyes, 40 eyes had a higher ablation depth (AD/CT ratio > 0.18) and 50 eyes had a lower ablation depth (AD/CT ratio < 0.18); 92.5% of eyes in the higher ratio group developed clinically significant haze (1+ or greater). In the lower ratio group, 94% of eyes developed no more than 1+ corneal haze, if any. CONCLUSION The ablation depth/corneal thickness ratio is useful for predicting corneal haze after LASEK. An AD/CT ratio of 0.18 or more suggests that patients have a high risk of developing clinically significant haze (1+ or more) after LASEK.

Cleavage of corneal basement membrane components by ethanol exposure in laser-assisted subepithelial keratectomy.

Purpose: To determine the anatomic cleavage plane after exposure to 20% ethanol for approximately 20 to 25 seconds to create an epithelial flap in laser‐assisted subepithelial keratectomy (LASEK). Setting: Ocular Surface Research & Education Foundation, Miami, Florida, and Hermann Eye Center Refractive Surgery Center, Houston, Texas, USA. Methods: Immunofluorescence staining using monoclonal antibodies against laminin 5, collagen VII, and integrins &bgr;1 and &bgr;4 was performed to determine the anatomic location of the cleavage plane in an epithelial flap created by 20‐second exposure to 20% ethanol in cadaver eyes and in epithelial flaps obtained from LASEK patients. Results: Immunofluorescence staining to laminin 5 and integrin &bgr;4 was patchy in the lifted flap and the remaining corneal basement membrane. Immunostaining to collagen VII, the main component of anchoring fibrils, remained exclusively in the corneal bed. Immunostaining to integrin &bgr;1, present in the pericellular location of all epithelial cell layers, remained exclusively in the epithelial flap. This finding was consistent in cadaver corneas and LASEK epithelial flaps. Conclusion: The cleavage plane of the ethanol‐induced corneal epithelial flap is located between the lamina lucida and the lamina densa of the basement membrane, where integrin &bgr;4 interacts with laminin 5 to form hemidesmosomes.