Initial studies using aliphatic beta-nitro alcohols for therapeutic corneal cross-linking.

PURPOSE: Corneal collagen cross-linking through UVA-riboflavin photochemistry (UVAR) has been shown to be an effective treatment for keratoconus and related keratectasias. In recent studies using sclera, the authors observed that short-chain aliphatic beta-nitro alcohols can cross-link collagenous tissue under physiologic conditions. Thus, this study was undertaken to evaluate these agents as potential pharmacologic alternatives to UVAR. METHODS: Porcine corneal strips (8 x 4 mm) and corneoscleral complexes were cross-linked using 1 to 100 mM 2-nitroethanol (2ne), 2-nitro-1-propanol (2nprop), and 3-nitro-2-pentanol (3n2pent) at pH 7.4, 34 degrees C. Cross-linking by UVAR was carried out for comparison. Thermal shrinkage temperature analysis was used to evaluate cross-linking effects, and changes in corneal light transmission were determined with a fiber-optic spectrophotometer. RESULTS: At 10 and 100 mM for 96 hours, initial shrinkage temperature (T(i)) was shifted by 3.3 degrees C (P < 0.001) and 9.8 degrees C (P < 0.001) for 2ne, 2.9 degrees C (P = 0.008) and 4.9 degrees C (P < 0.001) for 2nprop, and 3.8 degrees C (P = 0.003) and 4.9 degrees C (P < 0.001) for 3n2pent. Reacting at 1 mM through daily exchange of fluid over 7 days shifted T(i) by 3.8 degrees C (P < 0.001), 4.4 degrees C (P = 0.002), and 3.2 degrees C (P = 0.005), for 2ne, 2nprop, and 3n2pent, respectively. These shifts were greater than cross-linking using UVAR (T(i) = 1.9 degrees C; P = 0.012). In the blue light region (400-500 nm), transmission was decreased by 5.6% (P = 0.003), 2.1% (P = 0.260), and 0% (P = 0.428) for 2ne, 2nprop, and 3n2pent, respectively. CONCLUSIONS: beta-Nitro alcohols can induce corneal cross-linking in vitro better than the UVAR technique and can induce negligible effects on light transmission. These early results suggest that such compounds could be used as topical stiffening agents for keratoconus and related disorders.

Short chain aliphatic beta-nitro alcohols for corneoscleral cross-linking: corneal endothelial toxicity studies.

PURPOSE: Recent studies suggest that short chain aliphatic beta-nitro alcohols can cross-link corneoscleral tissue under physiologic conditions. The present study was conducted to determine the cytotoxic threshold for these agents in vitro and to draw comparisons to commonly used topical ophthalmic agents. METHODS: Primary cultures of bovine corneal endothelial cells were grown to confluence in 24- and 96-well plates using standard protocol. The cells were exposed to three beta-nitro alcohols, 2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol in a range of concentrations from 0.1 to 10 mM. After a 48-hour exposure, cell necrosis and apoptosis were evaluated using trypan blue, propidium iodide, and annexin V staining. In addition, a review of the ophthalmic literature was conducted to derive comparisons with agents commonly used in clinical practice. RESULTS: An all-or-none response was observed for each compound. Positive staining with trypan blue, propidium iodide, and annexin V occurred at identical concentrations. The most toxic of the group was 2-nitro-1-propanol. The cytotoxic level for 2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol was 3 mM (0.0273%), 1 mM (0.0105%), and 3 mM (0.0399%), respectively. Furthermore, by comparison with several agents used in ophthalmic practice such as fluoroquinolone antibiotics, anti-proliferative agents, and benzalkonium chloride, the beta-nitro alcohols exhibit less toxicity in vitro. CONCLUSIONS: Short chain aliphatic beta-nitro alcohols exhibit favorable in vitro toxicity thresholds. The result of this study encourages further evaluation of these compounds as potential pharmacologic topical stiffening agents for corneoscleral disorders.

Aliphatic beta-nitro alcohols for non-enzymatic collagen cross-linking of scleral tissue.

The success of riboflavin photochemical cross-linking of the cornea in treating keratoconus and post-surgical keratectasia has prompted interest in cross-linking scleral tissue with a potential application to stabilize myopic progression. Applying an UVA light source to the sclera is difficult, particularly in the posterior region. An alternate pharmacologic approach to scleral cross-linking may be possible. The present study was undertaken in order to identify nitrite related compounds capable of inducing scleral tissue cross-linking and to gain information regarding the possible chemical mechanisms involved. 8x4 mm strips of porcine and human sclera were incubated in various concentrations of nitrite related agents (1-100mM) at 37 degrees C. pH 7.4 was used for all experiments except those involving NaNO(2). Following a 24-96 h incubation period, the samples were tested for cross-linking effects using thermal shrinkage temperature (T(s)) analysis. Several compounds were studied including NaNO(2), 2-nitroethanol, 2-nitro-1-propanol, 3-nitro-2-pentanol, 2-nitrophenol, 2-nitroethane, 2-aminoethanol, isopentyl nitrite, DPTA/NO, DETA/NO, and urea, a nitrous acid trap. The results indicate that short chain aliphatic beta-nitro alcohols (2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol) are particularly effective cross-linking agents at pH 7.4, showing both time and concentration dependent effects. Furthermore, nitrosation does not appear to induce tissue cross-linking. In conclusion, aliphatic beta-nitro alcohols can cross-link scleral tissue at physiologic pH and temperature. Since beta-nitro alcohols are known to have reasonable toxicity profiles, these agents could find utility as pharmacologic cross-linking agents for scleral thinning disease.

Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac.

PURPOSE: To compare the incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated postoperatively with topical prednisolone and those treated with topical prednisolone and nepafenac 0.1% suspension (Nevanac). SETTING: Edward S. Harkness Eye Institute of Columbia University, New York, New York, USA. METHODS: This retrospective chart review was of consecutive patients who had phacoemulsification at a single institute and were given topical prednisolone alone or topical prednisolone and nepafenac to prevent cystoid macular edema. Data collection included preexisting ocular and systemic diseases, concurrent use of ocular and systemic medications, surgical technique, intraoperative and postoperative complications, follow-up visual and ocular assessments, and postoperative optical coherence tomography (OCT) assessment for macular edema. RESULTS: Postoperatively, 240 patients were treated with prednisolone and 210 patients, with prednisolone-nepafenac. Preoperatively, the 2 groups were demographically and clinically comparable in sex distribution (P = .8400), history of diabetes (P = .7267), hypertension or cardiac disease (P = .8690), and concurrent use of oral nonsteroidal anti-inflammatory drugs (P = .7303). Iris manipulation was done in 16 patients in the prednisolone-alone group and 10 patients in the prednisolone-nepafenac group (P = .3876). Capsule staining was done in 5 patients and 4 patients, respectively. All patients were followed for at least 1 month postoperatively. Visually significant pseudophakic macular edema was documented by OCT in 5 patients treated with prednisolone alone and in no patients treated with prednisolone and nepafenac (P = .0354). No significant intraoperative or postoperative complications were reported. CONCLUSION: Patients treated with topical prednisolone alone had a significantly higher incidence of visually significant pseudophakic macular edema after uneventful cataract surgery than those treated with topical prednisolone and nepafenac.

Scotopic sensitivity and color vision with a blue-light-absorbing intraocular lens.

PURPOSE: To investigate possible adverse effects of a yellow-tinted intraocular lens (IOL) on scotopic sensitivity and hue discrimination. SETTING: Departments of Ophthalmology, Columbia University and New York University School of Medicine, New York, New York, USA. METHODS: Nine patients with a yellow-tinted IOL in 1 eye and a colorless ultraviolet IOL in the fellow eye and 9 young phakic subjects with and without a yellow-tinted clip-on lens were tested. Hue discrimination was measured with the Farnsworth-Munsell (FM) 100-hue test. Dark-adapted thresholds to 440 nm, 500 nm, and 650 nm lights were measured at 23 locations using a modified Humphrey perimeter, and dark-adapted thresholds to white light were measured at 15 degrees temporal retina. RESULTS: In the 9 patients, there were no significant differences in dark-adapted sensitivities to 440, 500, 650 nm, or white-light stimuli and no differences in FM 100-hue error scores between eyes with yellow-tinted IOLs and those with colorless IOLs. Similarly, in young phakic subjects, there were no significant differences in FM 100-hue error scores or dark-adapted sensitivity to the white light with and without the yellow-tinted clip-on lens. However, with the clip-on lens, mean sensitivities to the 440 nm, 500 nm, and 650 nm stimuli were significantly decreased by 2.7 to 2.8 dB, 0.7 to 1.0 dB, and 0 to 1.2 dB, respectively. CONCLUSION: Results suggest that implantation of a yellow-tinted IOL has non-significant effect on scotopic sensitivity and hue discrimination.

Evaluating central corneal thickness measurements with noncontact optical low-coherence reflectometry and contact ultrasound pachymetry.

PURPOSE: To compare the central corneal thickness (CCT) measurements obtained with noncontact optical low-coherence reflectometry (OLCR) and ultrasound (US) pachymetry. DESIGN: Prospective, comparative observational study. METHODS: Three sequential ultrasonic measurements and a set of five OLCR scans of 52 eyes of 26 healthy subjects were recorded. Noncontact measurement was repeated five minutes after anesthetic drop instillation. RESULTS: Mean CCT values for noncontact OLCR and US pachymetry were 544.03 microm and 548.66 microm, respectively, with mean SDs of 0.97 microm and 4.63 microm, respectively. Noncontact OLCR measured on average 4.64 microm less than US pachymetry (95% confidence interval -7.56 to -1.72; P = .003). The OLCR measured 1.68 microm less than US pachymetry in the thinner cornea group (< or =548.7 microm, n = 24) and 7.48 mum less in the thicker group (n = 25). This difference was statistically significant (P = .04). CONCLUSIONS: There was agreement between the two pachymetric measurements. Noncontact OLCR appeared to measure slightly smaller than US pachymetry.

Accommodative spasm after laser-assisted in situ keratomileusis (LASIK).

PURPOSE: To report a case of accommodative spasm following laser-assisted in situ keratomileusis (LASIK). DESIGN: Observational case report. METHODS: Ophthalmic examination including manifest and cycloplegic refraction to assist in diagnosis. RESULTS: Two months following LASIK surgery, a 41-year-old healthy woman complained of intolerable headaches that had interfered with her daily activities. The patient sought medical consultation, and an MRI of the brain was normal. Best-corrected visual acuity (BCVA) was 20/20 and 20/25 with manifest refraction of -2.25 -0.50 x 170 and plano in the right and the left eye, respectively. Cycloplegic refraction was plano in the right and +0.75 sphere in the left eye, and she was corrected to 20/20 bilaterally. After being treated with cyclopentolate 1% one drop at bedtime to each eye for approximately six weeks, the headache completely resolved. CONCLUSIONS: Accommodative spasm should be considered in patients undergoing LASIK surgery complicated with fluctuating refraction of uncertain causes.

The effect of lubricant eye drops on ocular wavefront aberrations.

PURPOSE: To study the effect of lubricant eye drop instillation on ocular wavefront aberrations. METHODS: The wavefront aberrations of the entire optical path of 30 eyes of 15 patients before and following instillation of lubricant eye drops (Bion Tears; Alcon Laboratories Inc, Ft Worth, Tex) were obtained over a 6-mm pupil using a Hartmann-Shack wavefront sensor (WaveScan; VISX Inc, Santa Clara, Calif). Additional computation of root-mean-square (RMS) errors of higher order aberrations from third to sixth order were done using Zernike Tool Software (VISX Inc). Main outcome measures include the mean changes of total higher order aberrations RMS, higher order aberrations, and point spread function (PSF) of the higher order aberrations. RESULTS: The mean changes of total higher order aberrations following instillation of lubricant eye drops on the right eyes were -0.07 microm (95% confidence interval [CI], -0.11 to -0.03) and -0.03 microm on the left eyes (95% CI, -0.07 to 0.01). Significant mean changes were noted for coma and trefoil aberrations with a magnitude of -0.08 microm (95% CI, -0.12 to -0.03) and -0.09 (95% CI, -0.13 to -0.05), respectively, as well as a mean change of the PSF of the higher order aberrations (-0.05 diopters, 95% CI, -0.08 to -0.02) on the right eyes. Although no significant changes in these parameters were demonstrated on the left eyes, a similar trend of changes was observed. CONCLUSIONS: Ocular wavefront aberrations may change following eye drop instillation as measured objectively by the WaveScan system. This effect should be taken into consideration in the assessment of patients for wavefront-guided laser vision correction procedures.

Epithelial ingrowth under a laser in situ keratomileusis flap after phacoemulsification.

A 47-year-old man was referred to us for management of a cataract in the left eye. The patient had an ocular history of high myopia with anisometropia, amblyopia in the left eye, and stable myopic lattice degeneration in both eyes. The patient had successful bilateral laser in situ keratomileusis 3 years before and multiple retinal surgeries for treatment of a rhegmatogenous retinal detachment associated with a giant retinal tear in the temporal region of the retina with subsequent proliferative vitreoretinopathy. Phacoemulsification was performed uneventfully. A single interrupted 10-0 nylon suture was placed in the temporal clear corneal wound and removed 7 weeks postoperatively. One month later, slitlamp examination revealed a 1.5 mm tongue-like area of epithelial ingrowth under the corneal flap. The epithelial cells seemed to enter the flap-stroma interface through the previously placed suture tract and advanced centrally.

Corneal edema resolution after "descemetorhexis".

A 79-year-old woman had left eye phacoemulsification complicated by inadvertent excision of Descemet's membrane (DM). One day postoperatively, the visual acuity was counting fingers with diffuse corneal edema. The patient was treated medically, with gradual resolution of the corneal edema over a 6-month period. The torn edge of DM could be visualized as the edema cleared, and no endothelial cell count could be obtained centrally. Approximately 1 year postoperatively, the central endothelial cell count was 2114 cells/mm(2) in the right eye and 827 cells/mm(2) in the left eye. The decreased cell count, increased polymegethism, and pleomorphism suggested that endothelial cells migrated to cover the stromal surface area in the absence of DM.

Cataract surgery results after pars plana vitrectomy.

Continuous refinements in vitreoretinal surgical techniques and an increasing number of posterior segment disorders are being successfully managed with pars plana vitrectomy (PPV). This has resulted in an increase in the number of vitrectomized eyes seen by cataract surgeons. Cataract surgery in previously vitrectomized eyes has been reported to be more challenging than in eyes without previous vitrectomy. Special considerations and precautions are often required before, during, and after the surgery to successfully address these challenges. Several studies have reported that phacoemulsification with intraocular lens implantation after PPV is a relatively safe procedure that can improve visual acuity and quality of life. The extent of visual improvement may be limited only by retinal comorbidity.

Tegaderm transparent dressing (3M) for the treatment of chronic exposure keratopathy.

We report an effective alternative treatment of profound chronic exposure keratopathy in a proptotic eye due to intraorbital extension of basal cell carcinoma. The corneal surface gradually reepithelialized in a 6-week period after the first application of Tegaderm transparent dressing (3M, St. Paul, MN, U.S.A.) with instillation of antibiotic ointment on the ocular surface. The patient has been comfortable with an intact epithelial surface, a vascularized cornea, and nonirritated surrounding skin after changing the Tegaderm dressing daily for 15 months. There was no evidence of recurrent corneal ulceration or infiltrations. We conclude that Tegaderm represents a useful treatment of exposure keratopathy due to chronic proptosis.

Outcome of phacoemulsification after pars plana vitrectomy.

PURPOSE: To compare the outcome of phacoemulsification surgery in patients with and without prior vitrectomy, adjusted for confounding factors. DESIGN: Retrospective cohort study. PARTICIPANTS AND CONTROLS: Thirty-one consecutive eyes undergoing phacoemulsification after pars plana vitrectomy (PPV) and 116 consecutive eyes undergoing phacoemulsification without previous PPV. METHODS: Office records of the operating surgeons were reviewed for age, gender, type of cataract, vitrectomy status, best-corrected visual acuity (BCVA) before and after phacoemulsification, intraoperative difficulties, and postoperative complications. Bivariate analyses between these predictors and the main outcome, BCVA of 20/40 or better after phacoemulsification, were performed using Pearson's chi-square tests. An adjusted analysis of the relationship between outcome and vitrectomy status was performed with logistic regression. Pearson's chi-square tests were used to compare type of cataract, intraoperative difficulties, and postoperative complications in study and control eyes. MAIN OUTCOME MEASURES: BCVA of 20/40 or better after phacoemulsification, rates of intraoperative difficulties, and postoperative complications. RESULTS: The most common indication for PPV was macular hole. The average interval from PPV to phacoemulsification was 15.4 months. Study eyes were followed for an average of 10 months compared with 6.6 months for controls. Study eyes were more likely than controls to have predominantly nuclear sclerotic cataracts (P = 0.002). After cataract extraction, 24 of 31 study eyes (77.4%) and 110 of 116 control eyes (94.8%), had BCVAs of 20/40 or better. After adjusting for confounders, eyes without previous vitrectomy were 3.44 times more likely to obtain a BCVA of 20/40 or better than eyes with prior PPV, but this difference was not statistically significant (95% CI, 0.72-16.67). Only 3 of 31 (9.7%) study and 11 of 116 (9.4%) control eyes had intraoperative difficulties (P = 0.47). Posterior capsule plaque was the most common intraoperative difficulty in study eyes; small pupil requiring stretching or iris hooks was most common in controls. Only 1 of 31 (3.2%) study eyes had a postoperative complication other than posterior capsule opacification compared with 18 of 116 (15.5%) controls (P = 0.07). CONCLUSIONS: A large proportion of patients with prior PPV obtain good visual acuity after phacoemulsification. We did not find significantly higher rates of intraoperative difficulties or postoperative complications compared with controls. The benefits of phacoemulsification seem to be limited only by retinal comorbidity.