Robert J. Noecker

Corneal and conjunctival changes caused by commonly used glaucoma medications.

Purpose: To evaluate the extent of epithelial corneal and conjunctival changes associated with prolonged use of topical glaucoma medications. Methods: Thirty eyes of 15 New Zealand white rabbits were randomized to 1 of 6 treatment groups: artificial tears (Refresh Tears, carboxymethyl cellulose 0.5%) BID, brimonidine Purite® 0.15% BID, bimatoprost 0.03% QD, dorzolamide 2% BID, timolol maleate 0.5% BID, or latanoprost 0.005% QD for 30 days. Corneal damage was evaluated by scanning electron microscopy and graded on a standard scale by a masked observer. Conjunctival inflammation was evaluated with light microscopy, and inflammatory cells were counted in the epithelium and superficial and deep stroma by a masked observer according to a standard protocol. Results: In the cornea, artificial tears produced significantly less damage than dorzolamide or latanoprost (P = 0.001), and brimonidine Purite® produced significantly less damage than dorzolamide, timolol, or latanoprost (P = 0.001). The mean damage scores with bimatoprost were significantly lower than with dorzolamide, timolol, or latanoprost (P = 0.002). In the conjunctiva, the number of inflammatory cells in the epithelium was significantly lower in eyes treated with artificial tears or brimonidine Purite® than in eyes treated with timolol or latanoprost (P = 0.042). Conclusions: Although the adverse effects of glaucoma medications on the ocular surface are likely multifactorial, 1-month treatment with glaucoma medications containing higher levels of benzalkonium chloride (BAK) resulted in greater corneal damage and conjunctival cell infiltration than medications preserved with Purite® or with lower levels of BAK. Using glaucoma medications with alternative preservatives or low levels of BAK may help preserve ocular health.

Effects of common ophthalmic preservatives on ocular health.

Preservatives are an important component of ophthalmic preparations, providing antimicrobial activity in the bottle and preventing decomposition of active drug. Often underrecognized, however, are the significant cytotoxic effects of preservatives associated with long-term therapy and especially use of multiple preserved drugs. The most common preservatives in ophthalmic preparations for glaucoma and surface eye disease—benzalkonium chloride (BAK), chlorobutanol, sodium perborate, and stabilized oxychloro complex (SOC)—were reviewed. Compared with other preservatives, SOC caused the least amount of damage to rabbit corneal epithelial cells. BAK has demonstrated cytotoxic effects in cell culture, as well as in animal and human studies. Physicians should consider treatment with new-generation preparations containing low-risk preservatives such as SOC, especially in patients receiving multiple ophthalmic medications.

Effects of Age on Optical Coherence Tomography Measurements of Healthy Retinal Nerve Fiber Layer, Macula, and Optic Nerve Head

PURPOSE To determine the effects of age on global and sectoral peripapillary retinal nerve fiber layer (RNFL), macular thicknesses, and optic nerve head (ONH) parameters in healthy subjects using optical coherence tomography (OCT). DESIGN Retrospective, cross-sectional observational study. PARTICIPANTS A total of 226 eyes from 124 healthy subjects were included. METHODS Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT (Carl Zeiss Meditec, Dublin, CA). All global and sectoral RNFL and macular parameters and global ONH parameters were modeled in terms of age using linear mixed effects models. Normalized slopes were also calculated by dividing the slopes by the mean value of the OCT parameter for interparameter comparison. MAIN OUTCOME MEASURES Slope of each OCT parameter across age. RESULTS All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8 to 10, which were not statistically different from a slope of zero. Highest absolute slopes were in the inferior and superior quadrant RNFL and clock hour 1 (superior nasal). Normalized slopes showed a similar rate in all sectors except for the temporal clock hours (8-10). All macular thickness parameters statistically significantly decreased with increasing age, except for the central fovea sector, which had a slight positive slope that was not statistically significant. The nasal outer sector had the greatest absolute slope. Normalized macular slope in the outer ring was similar to the normalized slopes in the RNFL. Normalized inner ring had shallower slope than the outer ring with a similar rate in all quadrants. Disc area remained nearly constant across the ages, but cup area increased and rim area decreased with age, both of which were statistically significant. CONCLUSIONS Global and regional changes caused by the effects of age on RNFL, macula, and ONH OCT measurements should be considered when assessing eyes over time. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells

Introduction|To investigate potentially adverse effects of different topical glaucoma medications and preservatives on cultured ocular epithelial cells.Methods|Confluent cultures of human corneal (10.014 pRSV-T) and conjunctival cells (1-5c-4) were assayed with 100 μL of different glaucoma medications for 25 minutes at 37°C and 5% CO2. We also tested the preservative sofZia® (Alcon Laboratories, Fort Worth, TX, USA), as well as a range of concentrations of the preservative benzalkonium chloride (BAK; 0.001% to 0.050%). Balanced salt solution was used as the “live” control and a solution containing 70% methanol and 0.2% saponin was used as a “dead” control. The LIVE/DEAD viability/cytotoxicity kit (Invitrogen, Carlsbad, CA, USA) was used to determine the percentage of dead and live cells via ethidium homodimer and calcein fluorescence, respectively.Results|The toxicity of the prostaglandin analogs latanoprost, tafluprost and travoprost preserved with BAK was similar to the toxicity observed in their respective BAK concentrations. The prostaglandin analog travoprost (0.004%) preserved with the oxidizing preservative sofZia had much greater corneal and conjunctival cell survival than travoprost preserved with BAK. Travoprost (0.004%) containing polyquad also performed statistically better than its BAK-preserved formulation.Conclusion|Ocular surface side effects have previously been demonstrated with chronic, long-term exposure to intraocular pressurelowering medications containing the common preservative BAK. BAK alone has significant in-vitro cytotoxicity to cultured ocular epithelial cells. Substitution of BAK with polyquad or sofZia resulted in significantly higher percentages of live conjunctival and corneal cells. Further studies are needed to understand the- clinical implications of these findings.

Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofZia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears.

Purpose: To evaluate corneal and conjunctival changes after chronic, once-daily dosing of travoprost preserved with sofZia, latanoprost preserved with 0.02% benzalkonium chloride (BAK), or preservative-free artificial tears. Methods: Thirty New Zealand white rabbits were randomized to receive once-daily instillation of travoprost with sofZia, latanoprost, or preservative-free artificial tears in 1 eye. Corneal epithelial changes were evaluated by transmission electron microscopy and graded on a standard scale by 2 masked observers. Conjunctival inflammation was evaluated by light microscopy after hematoxylin and eosin staining. Lymphocytes were counted in the epithelium and superficial stroma by 2 masked observers and compared among groups. Results: Corneal tissue treated with preservative-free artificial tears and travoprost with sofZia revealed similar changes under transmission electron microscopy (P = 0.53). Significantly more corneal epithelial damage was noted with latanoprost than travoprost with sofZia (P = 0.0001). The number of lymphocytes in the conjunctival epithelium and stroma was significantly lower in eyes treated with travoprost with sofZia than eyes treated with latanoprost (P = 0.0001). The number of conjunctival lymphocytes was similar among conjunctival specimens exposed to travoprost with sofZia and preservative-free artificial tears (P = 0.65). Conclusions: Once-daily dosing of travoprost with sofZia produced significantly fewer corneal changes and less conjunctival inflammation than latanoprost preserved with BAK. Corneal and conjunctival changes noted with travoprost with sofZia were similar to those induced by preservative-free artificial tears. Glaucoma medication with high levels of BAK may cause more deleterious effects on the ocular surface than non-BAK-preserved medications. Human studies are needed to better understand the clinical effects of different preservative types and concentrations on the ocular surface.

Intravitreal Bevacizumab in a Patient With Neovascular Glaucoma

The utility of intravitreal bevacizumab injection in a patient with neovascular glaucoma following central retinal vein occlusion is explored. Bevacizumab (1 mg in 0.04 mL) was used after failed intraocular pressure (IOP) control with transscleral cyclophotocoagulation and panretinal photocoagulation. IOP improved within 2 days and the patient experienced marked improvement in comfort. Bevacizumab may be an effective medication for the treatment of neovascular glaucoma.

Effect of optic nerve head drusen on nerve fiber layer thickness

OBJECTIVE The purpose of the study was to evaluate the effect of optic nerve head drusen (ONHD) on nerve fiber layer (NFL) thickness by visual field testing, red-free photography of NFL, and optical coherence tomography (OCT). DESIGN The study design was a prospective clinical study. PARTICIPANTS Twenty-three eyes of 15 consecutive patients with ONHD and 27 eyes of 27 age-matched control subjects participated. INTERVENTION Ophthalmologic examination, color and red-free photography, automated Humphrey visual field testing, and OCT were performed. Each of the drusen study eyes were graded on a scale of 0 to III based on the amount of visible ONHD. Grade 0 represented the absence of clinically visible ONHD, and grade III represented an optic nerve head with abundant drusen. MAIN OUTCOME MEASURES Findings from clinical evaluation and color optic nerve head photographs and NFL evaluation by red-free photography, visual fields, and OCT were measured. RESULTS The number of study eyes with visual field defects increased with the higher grade drusen discs, corresponding both with progressively thinner NFL measurements by OCT and NFL loss shown by NFL photography. The NFL evaluation showed NFL thinning by red-free photography in 12 (71%) of 17 eyes with visible drusen (grades I-III discs) and visual field defects in 9 (53%) of 17 eyes in this group. By OCT measurements, the superior and inferior NFLs were significantly thinner in the eyes with visible ONHD compared with those of control eyes in the superior quadrant (P < 0.001) and inferior quadrant (P = 0.004). Compared with grade 0 discs, grades I through III discs showed statistically significant thinning of the NFL superiorly (P < 0.001). No statistical significant thinning of the NFL was seen in grade 0 discs compared with those of control subjects. CONCLUSIONS Optical coherence tomography is able to detect NFL thinning in eyes with ONHD and appears to be a sensitive and early indicator of NFL thinning. Increased numbers of clinically visible ONHD correlated with NFL thinning shown by OCT measurements and both visual field defects and NFL loss seen by red-free photography.

Needle Bleb Revision of Encapsulated Filtering Bleb With Bevacizumab

The utility of needle bleb revision with bevacizumab in a patient with a failing bleb following trabeculectomy is explored. The patient had previously failed needle bleb revision with mitomycin C. After needling and injection of 1 mg of bevacizumab, the bleb was noted to be more diffuse with a decrease in surface neovascularization. Bevacizumab may be an effective medication for rescuing failing filtering blebs that exhibit neovascularization.

Quantitative analysis of conjunctival goblet cells after chronic application of topical drops.

IntroductionChronic topical glaucoma therapy has been reported to cause deleterious changes to the ocular surface epithelial layers. We compare changes in the number of goblet cells after chronic exposure to latanoprost preserved with 0.02% benzalkonium chloride (BAK) eye drops (Xalatan®; Pfizer, NY, USA), travoprost preserved with sofZia® eye drops (Travatan Z®; Alcon, Fort Worth, TX, USA), or preservative-free artificial tears (Refresh Plus®; Allergan, Irvine, CA, USA).MethodsFifteen New Zealand white rabbits were randomised into groups of five (one eye was randomised for treatment) and received once-daily topical application of one of the three treatments for 30 days. Enucleation was performed at the end of the study followed by histologic analysis using mucin stains to identify goblet cells. Goblet cells were quantified and analysed using Student t tests to compare means between groups.ResultsGoblet cells per high-power field were 2.21 (±0.40) in the latanoprost with BAK group, 6.02 (±1.20) in the travoprost with sofZia group, and 7.03 (±1.33) in the preservative-free artificial tear group. The number of goblet cells in the latanoprost with BAK group was significantly lower than the other two groups (P=0.0001). There was no statistically significant difference in goblet cell numbers between the travoprost with sofZia and preservative-free artificial tear group (P=0.24).ConclusionOur study illustrates that, in this animal model, once-daily dosing of latanoprost with 0.02% BAK resulted in goblet cell loss compared with dosing with either travoprost with sofZia or preservative-free artificial tears.

A new quality assessment parameter for optical coherence tomography

Aim: To create a new, automated method of evaluating the quality of optical coherence tomography (OCT) images and to compare its image quality discriminating ability with the quality assessment parameters signal to noise ratio (SNR) and signal strength (SS). Methods: A new OCT image quality assessment parameter, quality index (QI), was created. OCT images (linear macular scan, peripapillary circular scan, and optic nerve head scan) were analysed using the latest StratusOCT system. SNR and SS were collected for each image. QI was calculated based on image histogram information using a software program of our own design. To evaluate the performance of these parameters, the results were compared with subjective three level grading (excellent, acceptable, and poor) performed by three OCT experts. Results: 63 images of 21 subjects (seven each for normal, early/moderate, and advanced glaucoma) were enrolled in this study. Subjects were selected in a consecutive and retrospective fashion from our OCT imaging database. There were significant differences in SNR, SS, and QI between excellent and poor images (p = 0.04, p = 0.002, and p<0.001, respectively, Wilcoxon test) and between acceptable and poor images (p = 0.02, p<0.001, and p<0.001, respectively). Only QI showed significant difference between excellent and acceptable images (p = 0.001). Areas under the receiver operating characteristics (ROC) curve for discrimination of poor from excellent/acceptable images were 0.68 (SNR), 0.89 (IQP), and 0.99 (QI). Conclusion: A quality index such as QI may permit automated objective and quantitative assessment of OCT image quality that performs similarly to an expert human observer.