What is on the horizon for cycloablation?

The concept of cycloablation has been present for several decades, but the inability to titrate a predictable and reproducible response has been its drawback. However, cycloablation still plays an important role in our paradigm of glaucoma therapy, since it can be the treatment of last resort for a small group of patients who have exhausted all other treatment modalities. Experience with argon or diode endolaser cyclophotocoagulation holds promise for these and other patients because it appears to demonstrate a safer side-effect profile, while providing good results. Better results may be partially due to visualization of the ciliary processes before applying laser energy, which allows for targeted destruction of tissue and limits the amount of inflammation. Additional experience will better define the indications and scope of these newer modalities.

Evaluating a visual field screening test for glaucoma: how the choice of the gold standard affects the validity of the test.

OBJECTIVE: To examine the effects of the gold standard on sensitivity, specificity, and area under the ROC curve when determining the validity of a screening test. METHODS: Fifty-eight people were recruited from a Veterans' Administration eye clinic. Screening included testing with the 26-point oculokinetic perimeter (OKP). We used different gold standards to categorize patients as positive or negative for glaucoma. The glaucoma hemifield test (GHT) and corrected pattern standard deviation (CPSD) from the Humphrey visual field analyzer (HVF) were used as objective gold standards. Ophthalmologist review of the HVF, using two different methods for classifying visual field defects, was also used as a gold standard. RESULTS: Using the review of the HVF that included mild, moderate, or severe defects, the area under the ROC curve was not significantly different from 50%. However, for all the other gold standards, the area under the ROC curve was significantly different from 50%. CONCLUSIONS: In determining the ability of the OKP to differentiate between glaucoma and normal subjects, the choice of a gold standard led to different conclusions about its usefulness as a screening test for glaucoma. Furthermore, sensitivity and specificity varied widely depending on which gold standard was used, and what cutoff point was used for the OKP. Although clinician review of the HVF may be used when specific criteria are given to define visual field defects, using objective measures from the HVF is easier and will allow for better comparisons between studies.

A survey of ocular complaints in postmenopausal women.

Aging patients often complain about chronic ocular irritation, which is commonly related to dryness of the eyes. To determine the effect of hormone replacement therapy (HRT) on ocular complaints and tear production, we compared these parameters in postmenopausal women who were taking or not taking HRT. A questionnaire was administered to determine the number of ophthalmic complaints of 79 women who were postmenopausal at least 1 year (mean, 22 +/- 13.5 years) and were not using any ophthalmic drops or medication known to contribute to dry eyes. A Schirmer test with anesthesia was performed on each subject to quantify tear production. We found that the number of ophthalmic complaints of women taking HRT was statistically fewer (P = 0.015) than women not taking HRT. Women taking HRT for 5 years or longer had statistically fewer complaints and greater tear production, as measured by the Schirmer test, than women taking HRT for 5 years or less. The study concluded that women taking HRT have significantly fewer ocular complaints than women not taking HRT. HRT may help alleviate symptoms related to ocular dryness in postmenopausal women.

Comparison of frequency doubling perimetry with humphrey visual field analysis in a glaucoma practice.

PURPOSE: To determine the sensitivity and specificity of frequency doubling perimetry with Humphrey visual field testing used as the gold standard. METHODS: Frequency doubling perimetry and Humphrey visual field testing (24-2) were performed on 29 consecutive patients in a glaucoma practice. Data for the right eye were used to calculate sensitivity, specificity, and receiver operating characteristic curves. RESULTS: For the frequency doubling perimetry in screening mode, and with an abnormal glaucoma hemifield test used as the gold standard, the area under the receiver operating characteristic curve was 89.3%, 81.5%, or 75.0% for the presence of mild, moderate, or severe relative defects, respectively. Similar results were found with the use of mean deviation (P <.05) to define Humphrey visual field defects. For frequency doubling perimetry in threshold mode, the area under the receiver operating characteristic curve was 93.4% with the presence of any defect (P <.05) used as the criterion for an abnormal case, and an abnormal glaucoma hemifield test as the gold standard. In all cases, the threshold mode detected defects better than the screening mode.

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group.

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Glaucomatocyclitic crisis in a child.

PURPOSE: To report a case of glaucomatocyclitic crisis (Posner-Schlossman syndrome) in a child. METHOD: Case report. A 13-year-old boy presented with decreased vision, photophobia, halos, and pain in the right eye. RESULT: Findings in this child were consistent with a diagnosis of Posner-Schlossman syndrome. CONCLUSION: Glaucomatocyclitic crisis can occur in a child and must be included in the differential diagnosis of uveitis and glaucoma in pediatric patients.

Effects of ascorbic acid on levels of fibronectin, laminin and collagen type 1 in bovine trabecular meshwork in organ culture.

PURPOSE: Fibronectin, laminin and collagen type I are important extracellular matrix products of trabecular meshwork cells. This study was performed to examine the effects of ascorbic acid, a significant component in the aqueous humor, on the levels of these proteins in trabecular meshwork cells maintained in organ culture. METHODS: The anterior segment of freshly enucleated bovine eyes was perfused in a modified organ culture system. Three cultures were set up simultaneously. One received serum-free medium containing 100 micrograms/ml of ascorbic acid, one received 250 micrograms/ml of ascorbic acid and one served as a control. After 72 h, the tissues were processed for paraffin sections and immunostaining was conducted using an avidin-biotin-peroxidase complex method. Western blot and dot blot assays were performed on tissue extracts. RESULTS: Compared with the controls, the staining for fibronectin and laminin was markedly enhanced in trabecular meshwork tissues treated with both concentrations of ascorbic acid. Increased collagen type I production by trabecular meshwork cells was also demonstrated in the presence of ascorbic acid. Western blot and dot blot results confirmed the immunostaining findings. CONCLUSIONS: Ascorbic acid promotes production of fibronectin, laminin and collagen type I by trabecular meshwork cells. The organ culture results are consistent with those obtained previously from tissue culture studies.

Transconjunctival mitomycin C as an adjunct to conventional glaucoma filtration surgery in rabbits.

PURPOSE: Subconjunctival mitomycin C has been used in glaucoma filtration surgery with success. A prospective, randomized, masked, placebo-controlled study was performed to evaluate whether single transconjunctival mitomycin C applied either preoperatively or postoperatively would enhance the success of filtration surgery in rabbits. METHODS: Two groups of 5 rabbits were studied. In Group I, a Weck-Cel sponge soaked in 0.5 mg/ml mitomycin C was applied transconjunctively for 7 minutes immediately before a full thickness filtering procedure. The other eye was treated similarly with a sponge soaked in balanced salt solution. Group II first underwent filtration surgery followed by treatment with either mitomycin-c or balanced salt solution 3 days later. Postoperative intraocular pressure, bleb status, and complications were evaluated. Treatment failure was defined as postoperative pressure within 4 mmHg of that determined preoperatively or the absence of bleb formation. RESULTS: In Group I, mean time to failure (+/- SD) was significantly longer (p = 0.03) in experimental eyes (30 +/- 15.1 days) than control eyes (8.6 +/- 0.8 days). In Group II, the time to failure was 12.4 (+/- 2.6) days versus 9.6 (+/- 2.5) days in the experimental and control eyes respectively, but this was not statistically significant (p = 0.10). Transient limbal vascularization and corneal haze were seen in all experimental eyes. Serious complications included late bleb rupture in eyes pretreated with mitomycin C (all eyes in Group I) and corneal decompensation (one mitomycin-c eye). CONCLUSIONS: This study demonstrates that a single preoperative tranconjunctival application of mitomycin-c is more effective at the time of surgery than an application applied in the intermediate postoperative period. Additional studies are needed, however, to further refine both the dose and timing of mitomycin-c application during filtration surgery.

Glaucoma: a preventable cause of blindness.

Glaucoma is a leading cause of blindness within the United States and the leading cause of blindness among African-Americans. Measurement of intraocular pressure only is no longer considered adequate for screening. Recognition of risk factors and examination of the optic nerve are key strategies to identify individuals at risk. Medical and surgical treatment of glaucoma have significantly improved in recent years. Early diagnosis and appropriate therapy will aid in reducing the potential of irreversible blindness.

In vitro evaluation of antiproliferative potential of calcium channel blockers in human Tenon's fibroblasts.

The calcium cation has been known to play a central and diverse role in the proliferation of numerous types of cells including fibroblasts. Therefore, ib1p4llows that calcium channel blockers (CCBs) may potentially inhibit fibroblast attachment and proliferation. The time and dose-related effects of five commonly used CCBs-verapamil, diltiazem, nicardipine, trifluoperazine, and dantrolene-on human Tenon's fibroblast attachment and proliferation were studied. Fibroblasts were incubated with different concentrations of each drug. To evaluate the effect of each drug on fibroblast attachment, cell density was quantified by Coulter counter and hexosaminidase assays after 24 hours of incubation. To evaluate the effect of each drug on fibroblast proliferation, cell density was quantified by Coulter counter, hexosaminidase, and 3H-thymidine uptake assays on days 1, 3, and 7. Dantrolene had minimal effect, failing to cause even 20% inhibition at 10(-5) M, the highest concentration tested. Verapamil, diltiazem, nicardipine, and trifluoperazine all inhibited fibroblast attachment and proliferation. Trifluoperazine was the most potent inhibitor of attachment and proliferation with ID50S in the 10(-5) M range. Verapamil, diltiazem, and nicardipine had similar potency in inhibiting attachment and proliferation with ID50S in the 10(-4) M range. Because CCBs seem to inhibit fibroblast attachment and proliferation, future clinical studies may show that these agents reduce collagen production, scar formation, and bleb failure following glaucoma filtration surgery.

Vasoactive intestinal peptide stimulation of human trabecular meshwork cell growth.

PURPOSE: To demonstrate that vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, is a growth factor of human trabecular meshwork (TM) cells in culture and in a corneoscleral explant organ culture treated with laser trabeculoplasty (LTP). METHODS: Proliferating human TM cells in cell cultures were incubated with VIP for 20 hours, followed by total cell number determination, using a Coulter counter. The percentage of proliferating TM cells was assessed, using an antibody against the proliferating cell nuclear antigen (PCNA). To test the growth effect of VIP on TM cells in situ, corneoscleral explants in organ cultures were first treated with argon LTP to initiate TM-cell proliferation and then were exposed to VIP for 48 hours. The mitotic TM cells were demonstrated immunocytochemically, using anti-PCNA in paraffin sections of the explants; and the total number of TM cells was determined after paraffin sections were counterstained by hematoxylin. RESULTS: Vasoactive intestinal peptide dose-dependently stimulated the proliferation of TM cells in cell culture. Treatment with 5 x 10(-10) M VIP resulted in a maximal increase of 40% in cell number. The effect of VIP was blocked by a VIP antagonist. The number of PCNA-stained TM cells and the total cell number in the TM in LTP-treated corneoscleral explants were increased by VIP. CONCLUSIONS: Exogenously applied VIP stimulated the proliferation of human TM cells in subconfluent cultures and in LTP-treated corneoscleral explants. In that LTP has been shown to increase the number of TM cells in situ, the growth stimulatory effect of VIP may help enhance this therapy.