In vitro characteristics of Tenon's fibroblast lines derived from pediatric and adult eyes do not fully explain pediatric glaucoma surgery failure: a preliminary report.

PURPOSE: To compare the in vitro characteristics of Tenon's capsule fibroblasts from children and adults that may be relevant to filtration surgery success. METHODS: Fibroblast cell lines derived from 5 young (median patient age, 2.4 years) and 7 old (median patient age, 71 years) discarded Tenon's capsule surgical specimens were used at early passage (P2-P3). Fibroblasts were plated at "high" (10(4)cells/cm(2)) or "low" density (10(3)cells/cm(2)) and harvested at days 0-14, for growth curve and doubling time comparisons. Migration was measured using a wound model (confluent monolayers ± 5-fluorouracil [5-FU] over 1-96 hours). Collagen synthesis was measured as secreted hydroxyproline/24 hours from confluent monolayers. RESULTS: At low density, "young" fibroblasts achieved higher cell numbers at confluence (day 14) compared with "old": 158 ± 35 versus 105 ± 12 × 10(3)cells/cm(2) (P = 0.0034). Mean doubling time for young versus old was similar at low density plating: 20.95 ± 1.55 versus 22.37 ± 2.09 hours (P = 0.26). It was shorter, however, for young versus old at high-density plating: 42.11 ± 6.01 versus 54.26 ± 4.24 hours (P = 0.0051). Wound closure rates were similar for young versus old cells (4 lines for each group) with and without 5-FU. Collagen synthesis was similar for young and old (4 lines for each group). CONCLUSIONS: Although young fibroblasts reached higher density than old at confluence and had shorter doubling times at high-density plating, wound closure/migration and collagen synthesis rates were similar. Despite the preliminary nature of this study (few specimens, limited cell features explored), factors besides those intrinsic to the fibroblasts themselves likely mediate the more rapid healing/scarring after glaucoma filtration surgery in children.

In vitro and in vivo comparison of two suprachoroidal shunts.

PURPOSE: To compare fibrosis, aqueous humor dynamics, and intraocular pressure (IOP) of two suprachoroidal shunts as part of a new class of glaucoma drainage devices. METHODS: Following proliferation analysis in vitro, 20 rabbits were implanted with either a gold shunt (GS, GMSplus+, SOLX) or a polypropylene shunt (PS, Aquashunt, OPKO). Ten eyes received mitomycin C (MMC) and triamcinolone. Peak and trough IOP were monitored with a pneumatonometer and tono-pen for 15 weeks. Aqueous humor dynamics were evaluated fluorophotometrically and tonographically. Fibrosis was quantified. RESULTS: In vitro proliferation was similar. In vivo, both shunts were devoid of foreign body reaction but exhibited fibrosis, and GS showed vascularization. There was no significant difference in aqueous or uveoscleral flow. Preoperative morning IOP was 23.7 ± 2 mm Hg, and evening IOP was 26.5 ± 2 mm Hg (P = 0.000). Morning IOP was decreased through 15 weeks and evening IOP through 8 weeks in all groups. The morning IOP decrease was most profound at 15 weeks in PS (41%) compared to GS (18%). Antifibrotics initially enhanced but eventually diminished shunt performance. At 15 weeks, thickness of scleral fibrosis was greater in GS (246 ± 47 µm) and PS (188 ± 47 µm, P = 0.285) compared with GS+MMC (109 ± 26 µm, P = 0.023 to GS) and PS+MMC (48 ± 30 µm, P = 0.028 to PS). CONCLUSIONS: In a rabbit model, suprachoroidal polypropylene and gold shunts allow access to a new drainage pathway with different IOP profiles that can be modified with antifibrotics.

Does titration of mitomycin C as an adjunct to trabeculectomy significantly influence the intraocular pressure outcome?

PURPOSE: To evaluate the benefit of titrating the concentration and exposure time of mitomycin C (MMC) as an adjunct to trabeculectomy. METHODS: This report consists of a retrospective study and a review of the literature. In the study, consecutive glaucoma patients were evaluated who underwent trabeculectomy with adjunctive MMC that was titrated for concentration and exposure time, based on patient's risk factors for surgical failure. After minimum follow-up of 6 months, patients were divided into success (intraocular pressure 7-17 mmHg), hypertension (>17 mmHg) and hypotony (<7 mmHg) groups, which were compared with regard to MMC protocol and patient variables. The literature review included reports of trabeculectomy and adjunctive MMC with and without titration. RESULTS: One hundred and fifty-five eyes of 155 patients were studied. There were no significant differences between the three outcome groups and MMC protocol (p > 0.05). The only significant patient variable was older age in the hypotony group (p = 0.009). The literature is conflicting regarding the value of titrating MMC as an adjunct in trabeculectomy. CONCLUSION: The outcome of trabeculectomy with adjunctive MMC appears to represent a complex interaction of patient and surgical variables. While there is some support for a benefit of titrating MMC according to individual patient variables, there is inadequate evidence at the present time to claim superiority for any MMC protocol, with or without titration.

Assessment of optic nerve cup-to-disk ratio changes in patients receiving multiple intravitreal injections of antivascular endothelial growth factor agents.

PURPOSE: To assess whether the transient intraocular pressure rise, frequent intraocular pressure fluctuations, or antivascular endothelial growth factor (VEGF) effects of repeated intravitreal injection of anti-VEGF agents can lead to changes in the optic nerve vertical cup-to-disk ratio (C/D). METHODS: Patients with a known history of glaucoma and those receiving triamcinolone acetonide were excluded from the study. Fundus photographs were cropped to optic disk images only, which were then randomized and independently graded by two glaucoma specialists. In patients who received treatments in only one eye, the fellow eye was used as a control. RESULTS: Twenty-three eyes of 21 patients met inclusion criteria. The mean change in C/D was -0.012 (95% confidence interval [CI], -0.053 to 0.029) for the treated group and -0.006 (95% CI, -0.106 to 0.095) for the control group, with no statistically significant difference (P = 0.90). The mean change in C/D for eyes receiving < or =5 injections (n = 9) was 0.003 (95% CI, -0.089 to 0.095) in the treated group and 0.054 (95% CI, -0.033 to 0.142) in the control group, with no statistically significant difference (P = 0.33). In eyes receiving >5 injections (n = 14), the mean change in C/D was -0.021 (95% CI, -0.095 to 0.052) in the treated group and -0.057 (95% CI, -0.231 to 0.116) in the control group, with no statistically significant difference (P = 0.70). CONCLUSION: There was no statistically significant change in the vertical C/D of optic nerves in patients receiving multiple intravitreal injections of anti-VEGF agents, regardless of whether they received fewer or more than five total injections. This suggests that the short-term intraocular pressure rise and frequent intraocular pressure fluctuation, as well as the anti-VEGF properties of these drugs, do not adversely change the optic nerve C/D. Additional prospective studies are warranted to confirm these conclusions.

Side effects associated with prostaglandin analog therapy.

Topical prostaglandin analogs, which have become first-line therapy in the medical management of glaucoma, have an excellent safety profile with regard to systemic side effects, but are associated with several ocular side effects. Some of these are common, with no apparent serious consequences other than cosmetic, whereas others are much less common but represent potentially sight-threatening side effects. The former group includes conjunctival hyperemia, elongation and darkening of eyelashes, induced iris darkening, and periocular skin pigmentation. The latter group of side effects, which are relatively rare and lack definitive causal relationship to prostaglandin analog therapy, includes iris cysts, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis. Most of the literature regarding side effects associated with prostaglandin analogs involves the use of latanoprost, probably because it was the first to be studied. There is no evidence, however, aside from less conjunctival hyperemia with latanoprost, that the commercially available prostaglandin analogs differ significantly with regard to side effects.

Iridocorneal endothelial syndrome in a child.

The iridocorneal endothelial syndrome is an important and unusual cause of acquired glaucoma in adults. We report its occurrence in a child who presented with glaucoma. The patient required glaucoma surgery, and a goniotomy and trabeculectomy were performed. The patient's clinical findings and the results of surgeries are described.

Factors associated with failure to follow up after glaucoma screening: a study in an African American population.

PURPOSE: To evaluate variables associated with failure to access free eye care after participating in glaucoma screening. DESIGN: Review of responses to a survey completed by participants during glaucoma screening. PARTICIPANTS: Two hundred seventy-three surveys completed by participants of African descent during screening. METHODS: African Americans 40 years or older participated in community glaucoma screening clinics, which included a survey with demographic and social variables. Each participant was given a preliminary diagnosis and encouraged to attend a free eye clinic for a complete examination. Survey results were correlated with attendance at the follow-up examination, using Student's t test, chi-square test, and logistic regression analysis. MAIN OUTCOME MEASURE: Noncompliance with follow-up after glaucoma screening. RESULTS: When adjusting for risk factors in logistic regression analysis, noncompliance was associated with living alone (P = 0.008), smoking (P = 0.0005), and lacking a car (P<0.01). Odds of noncompliance for participants living alone were 2.2 times higher than those for participants not living alone. Odds of noncompliance for participants who smoked were 3.0 times greater than those for participants who did not smoke. Odds of noncompliance for participants who did not have access to a car for their last eye examination were 2.1 times greater than those for participants who did. CONCLUSION: Socioeconomic factors such as smoking, lack of access to a car for eye examinations, and living alone are associated with noncompliance to follow-up after glaucoma screening clinics. Identifying persons with these variables may facilitate improved compliance.

The influence of peripheral iridotomy on the intraocular pressure course in patients with pigmentary glaucoma.

PURPOSE: To evaluate the influence of laser peripheral iridotomy on the long-term intraocular pressure course for patients with pigmentary glaucoma. PATIENTS AND METHODS: Retrospective analysis of data contributed by members of the American Glaucoma Society on patients with bilateral pigmentary glaucoma, who received uniocular laser iridotomy. The main outcome measure was the post-laser intraocular pressure course of the treated eyes, compared with the fellow, untreated eyes. RESULTS: Sixty patients were included in the study, 46 of whom were observed for a minimum of 2 years (mean 70.3 +/- 26.0 months; range 24-113 months). Among the 14 patients who were observed for less than 2 years, the mean intraocular pressure in the treated eyes increased 0.36 +/- 2.63 mm Hg, compared with the fellow, untreated eyes. Among the 46 patients, observed for 2 years or more, the mean intraocular pressure in the treated eyes decreased 4.0 +/- 5.4 mm Hg, compared with 1.9 +/- 3.8 mm Hg in the fellow eyes (P = 0.005). However, analysis by linear models indicates that a higher mean baseline intraocular pressure in the treated eyes accounts for the apparent treatment effect of laser peripheral iridotomy. CONCLUSION: The study does not provide support for the benefit of laser peripheral iridotomy in the long-term intraocular pressure control of patients with pigmentary glaucoma, when the data are subjected to rigid statistical analysis. This does not disprove the benefit of laser iridotomy in this patient population, but underscores the need for a large, prospective study to address the question.

Considerations of glaucoma in patients undergoing corneal refractive surgery.

Glaucoma patients present a unique set of challenges to physicians performing corneal refractive surgery. Corneal thickness, which is modified during corneal refractive surgery, plays an important role in monitoring glaucoma patients because of its effect on the measured intraocular pressure. Patients undergo a transient but significant rise in intraocular pressure during the laser-assisted in situ keratomileusis (LASIK) procedure with risk of further optic nerve damage or retinal vein occlusion. Glaucoma patients with filtering blebs are also at risk of damage to the bleb by the suction ring. Steroids, typically used after refractive surgery, can increase intraocular pressure in steroid responders, which is more prevalent among glaucoma patients. Flap interface fluid after LASIK, causing an artificially low pressure reading and masking an elevated pressure has been reported. The refractive surgeon's awareness of these potential complications and challenges will better prepare them for proper management of glaucoma patients who request corneal refractive surgery.

Needle revision of failed filtering blebs using 5-Fluorouracil and a combined ab-externo and ab-interno approach.

PURPOSE: To evaluate a surgical technique to revise a failed filtering bleb using subconjunctival 5-Fluorouracil with a combined ab-externo and ab-interno approach. PATIENTS AND METHODS: This study is a retrospective review of the outcome of 77 consecutive bleb revisions, with greater than 6-month follow-up, performed by a single glaucoma surgeon (MW). All eyes had previously functioning filtering blebs with currently inadequately controlled intraocular pressures (IOP) prior to the bleb revisions. All surgery was performed in the operating room, using a retrobulbar injection and a microscope. Visco-elastic was injected into the anterior chamber. 5-Fluorouracil (0.1 mL; 50 mg/ml) was infiltrated around the bleb. A 30-gauge needle was used to lyse subconjunctival fibrosis and episcleral scar tissue binding down the scleral flap, and elevate the scleral flap. Through an inferior paracentesis, a cyclodialysis spatula was used to confirm and enlarge the communication with the subconjunctival space. The main outcome measurements were IOP and number of glaucoma medications. A successful outcome was defined as a 20% reduction from baseline IOP and a maximum IOP of 18 mm Hg, with or without medications, and a minimal follow-up of 6 months. RESULTS: 52% of patients achieved success after one revision with an average follow-up of 29.6 +/- 14.4 months. In successful cases, the mean IOP decreased from 22.7 +/- 4.5 mm Hg to 11.3 +/- 3.5 mm Hg and medications were reduced from an average of 2.2 +/- 1.1 to 0.4 +/- 0.7. Kaplan-Meier survival analysis calculated a success of 77% at 1 year, 68% at 2 years, and 58% at 3 years. CONCLUSIONS: In failed filtering blebs, needle revision with 5-Fluorouracil and a combined ab-externo and ab-interno approach results in high success and low complication rates. The outcome of this procedure compares favorably with previously reported revision techniques.

Bleb revision for hypotony maculopathy after trabeculectomy.

PURPOSE: To assess the efficacy of a bleb revision technique with regard to improvement in intraocular pressure (IOP) and visual acuity after hypotony maculopathy and to evaluate the influence of duration of hypotony on visual outcome. PATIENTS AND METHOD: : Retrospective review of a series of patients who underwent bleb revision for hypotony maculopathy (IOP less than 6 mm Hg and loss of two or more lines of central vision) following trabeculectomy. Bleb revision included excision of avascular bleb tissue, dissection posteriorly between conjunctiva and Tenon's capsule, and advancement and suturing of the conjunctiva at the limbus. RESULTS: Fourteen patients were included in the study. The average age was 49.8 years (range 18-85) and eight were female. Before trabeculectomy, the mean IOP was 23.2 +/- 11.8 mm Hg, and the visual acuity was 20/30-2 or better in 13 patients and 20/80 in one patient. The mean IOP before bleb revision was 1.07 +/- 0.73 mm Hg, and 12 patients had lost an average of 4.33 +/- 2.96 lines of visual acuity from baseline, while one had count fingers and another had hand motion vision. The final mean IOP after bleb revision was 11.07 +/- 3.08 mm Hg. Compared with visual acuity just prior to bleb revision, 12 patients regained an average best corrected vision of 3.08 +/- 2.67 lines, with seven returning to the pre-trabeculectomy vision level. The duration of hypotony prior to bleb revision was 1 to 24 months (average 8.36 months) with no correlation (correlation coefficient -0.13) between duration and visual outcome. CONCLUSION: Bleb revision for hypotony maculopathy following trabeculectomy is an effective technique for raising IOP and limiting visual loss, which is not influenced by duration of hypotony within the time frame of the study.

Effect of mild to moderate myopic correction by laser-assisted in situ keratomileusis on intraocular pressure measurements with goldmann applanation tonometer, tono-pen, and pneumatonometer.

PURPOSE: To evaluate the effect of mild to moderate myopic correction by laser-assisted in situ keratomileusis (LASIK) on intraocular pressure (IOP) measurements with three tonometers: the Goldmann applanation tonometer, Tono-Pen, and pneumatonometer. PATIENTS AND METHODS: In a prospective study of a clinic-based population undergoing elective LASIK surgery for myopia correction, IOP measurements were obtained preoperatively and postoperatively with a Goldmann applanation tonometer, Tono-Pen, and pneumatonometer. Central corneal thickness and keratometric and astigmatism measurements were also obtained before and after surgery. A paired test was used to evaluate the significance of differences between preoperative and postoperative IOP measurements with each instrument. Linear regression was used to correlate IOP measurements with degree of myopia corrected, astigmatism, and central corneal thickness before and after surgery. RESULTS: The study included 66 eyes of 34 individuals with a mean preoperative refractive error of -5.66 + 2.3 D (mean + SD). The reduction of central corneal thickness after LASIK of 0.032 + 0.030 mm (mean + SD) was statistically significant ( < 0.0001). However, there was no statistically significant change in mean IOP after the procedure with the Goldmann applanation tonometer or the Tono-Pen, while the pneumatonometer, was associated with a small but statistically significant decrease in mean IOP of 1.1 mm Hg. CONCLUSION: In this group of patients with mild to moderate myopia, LASIK had little or no statistically significant influence on IOP readings obtained with a Goldmann applanation tonometer, Tono-Pen, or pneumatonometer. This finding is in contrast to earlier reports of greater amounts of myopic correction, in which significant reductions in measured IOP were observed. Further study is needed to determine whether a critical amount of corneal change after LASIK is required to have a significant effect on IOP measurements.