Epinephrine, but not dexamethasone, induces apoptosis in retinal pigment epithelium cells in vitro: possible implications on the pathogenesis of central serous chorioretinopathy.

BACKGROUND: The pathogenesis of central serous chorioretinopathy is poorly understood. It is believed to be due to dysfunction of the retinal pigment epithelium and/or choroid and has been associated with elevated levels of epinephrine and administration of corticosteroids. Epinephrine and corticosteroids have previously been shown to induce apoptosis (programmed cell death) in various types of cells. The objective of this study was to investigate whether these agents can induce apoptosis in cultured retinal pigment epithelium cells. This may help elucidate the pathogenesis of central serous chorioretinopathy. METHODS: Third-passage porcine retinal pigment epithelium cells were grown to confluence and incubated for 1-7 days in culture medium containing epinephrine (10(2)-10(9) pg/ml) or a corticosteroid, dexamethasone (4-4x10(4) ng/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. RESULTS: Epinephrine (7x10(7)-10(9) pg/ml) induced apoptosis in a dose- and time-dependent manner. Exposure to lower concentrations of epinephrine (10(2)-6x10(7) pg/ml) and all tested levels of dexamethasone did not result in apoptosis. CONCLUSION: Retinal pigment epithelium cells may undergo apoptosis following exposure to elevated levels of epinephrine. These findings suggest a possible pathophysiologic mechanism for the development of central serous chorioretinopathy.

Q-switched 532-nm Nd:YAG laser trabeculoplasty (selective laser trabeculoplasty): a multicenter, pilot, clinical study.

OBJECTIVE: To investigate the safety and efficacy of a new laser procedure using a q-switched 532-nm neodymium (Nd):YAG laser, also called "selective laser trabeculoplasty," to lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG). The laser parameters were set to selectively target pigmented trabecular meshwork (TM) cells without coagulative damage to the TM structure or nonpigmented cells. DESIGN: Nonrandomized, prospective, clinical trial. PARTICIPANTS: Thirty eyes of 30 patients with uncontrolled OAG (OAG group) and 23 eyes of 23 patients with uncontrolled OAG treated previously with argon laser trabeculoplasty (ALT group) were observed for 4 to 26 weeks. Forty-four of the 53 eyes were observed for 26 weeks. INTERVENTION: Patients were treated with the Coherent Selecta 7000 (Coherent, Inc, Palo Alto, CA) frequency-doubled q-switched Nd:YAG laser (532 nm). A total of approximately 50 nonoverlapping spots were placed over 180 degrees of the TM at energy levels ranging from 0.6 to 1.2 mJ per pulse. After surgery, patients were maintained with the identical drug regimen as that before treatment. RESULTS: Both the OAG and ALT groups showed similar IOP reductions over time. Seventy percent of patients in each group responded to treatment with an IOP reduction of least 3 mmHg. At 26 weeks of follow-up, mean IOP reduction was 5.8 mmHg (23.5%, P < 0.001) for the OAG group and 6.0 mmHg (24.2%, P < 0.001) for the ALT group. The untreated eye showed a 9.7% (P < 0.001) reduction of IOP at 26 weeks. However, the IOP difference between the treated and untreated eyes was statistically significant at P < 0.003. Transient IOP elevation of 5 mmHg or greater was seen in 24% of patients. CONCLUSION: The selective laser trabeculoplasty appears to be a safe and effective method to lower IOP in patients with OAG and patients treated previously with ALT. A reduction of IOP can be achieved without coagulation of the TM.

Apoptosis and morphologic changes in drug-treated trabecular meshwork cells in vitro.

Using an in vitro culture system, we investigated whether bovine trabecular meshwork cells undergo apoptosis (programmed cell death) following exposure to anti-glaucoma medications (timolol, pilocarpine and epinephrine) and known inducers of apoptosis (5-fluorouracil, mitomycin-C and dexamethasone). Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1-12 days in growth media with timolol (1-1000 microM), pilocarpine (15-15,000 microM), epinephrine (5-5000 microM), 5-fluorouracil (10-100 micrograms ml-1), mitomycin-C (0.01-100 micrograms ml-1) and dexamethasone (0.01-100 microM). The cultures were evaluated for apoptosis by phase-contrast microscopy, transmission electron microscopy and in situ apoptosis labeling. 5-Fluorouracil (10-100 micrograms ml-1), mitomycin-C (0.1-100 micrograms ml-1) and epinephrine (500-5000 microM) induced apoptosis in a dose and time-dependent manner. Timolol, pilocarpine, and dexamethasone-treated specimens did not show evidence of apoptosis at any of the concentrations tested. Trabecular meshwork cells incubated in timolol (100-1000 microM) developed cytoplasmic granules, and specimens treated with pilocarpine (15,000 microM) developed cytoplasmic vacuoles. These granules and vacuoles have the appearance of secondary lysosomes. Dexamethasone-treated cells developed an increased number of mitochondria. This study suggests that the trabecular meshwork may undergo apoptosis following exposure to 5-fluorouracil, mitomycin-C and epinephrine. Timolol, pilocarpine and dexamethasone did not induce apoptosis. However, these drugs can incite characteristic morphologic changes in cultured trabecular meshwork cells.

Chorioretinal folds following glaucoma valve implantation.

Glaucoma valve implants have been observed to cause scleral indentation and flattening. The authors report the case of a 79-year-old woman who had previously undergone glaucoma valve implantation, and who subsequently developed chorioretinal folds that corresponded to the implant in location and configuration. Accumulation of fluid behind the implant, as documented by B-scan ultrasonography, appeared to result in the observed scleral and chorioretinal changes. The authors conclude that chorioretinal folds can result following glaucoma valve implantation.

The use of processed pericardium in the repair of corneo-scleral fistulas.

Explantation of glaucoma valve implants may be complicated by wound closure problems. Prolonged implantation of these valves can lead to development of corneo-scleral fistulas that may not be adequately sealed with the use of sutures alone. The authors report the use of processed pericardium as tissue replacement material for the repair of such fistulas. A 45-year-old woman underwent explantation of a Baerveldt glaucoma valve implant, resulting in the development of a corneo-scleral fistula. To repair the fistula, processed pericardium was inserted into it and secured with 10-0 nylon sutures. Postoperatively, a good wound seal was achieved with no leakage of aqueous humor from the anterior chamber, nor any inflammation. Processed pericardium appears to be an effective tissue replacement material for sealing corneo-scleral fistulas.

Cataract extraction as a means of treating postfiltration hypotony maculopathy.

Hypotony maculopathy may arise after glaucoma filtering surgery. This can be treated by inducing inflammation and scarring within the filter, with the aim of increasing intraocular pressure (IOP) and promoting resolution of maculopathy. Cataract extraction can promote such inflammation. Phacoemulsification with posterior chamber intraocular lens (PC IOL) implantation was performed in two consecutive patients with postfiltration hypotony maculopathy and preexisting cataracts. After cataract extraction, improvement of IOP, visual acuity, maculopathy, and metamorphopsia occurred in both patients. Cataract extraction can be beneficial in the management of postfiltration hypotony maculopathy.

Midterm reversible failure in trabeculectomies with adjunctive mitomycin-C.

BACKGROUND AND OBJECTIVES: Trabeculectomies usually fail early (< 21 days) or late (> 6 months) when no antifibrotic agent is used. Failure is uncommon during the midterm period, between 3 weeks and 6 months. The purpose of this study is to verify the incidence of failure of trabeculectomies with mitomycin-C (MMC) during the midterm period and to evaluate the safety and efficacy of laser suture lysis (LSL) for reversing it. PATIENTS AND METHODS: The authors reviewed the records of 130 consecutive patients who underwent trabeculectomy with adjunctive MMC. RESULTS: Fourteen patients (15 eyes) had increased intraocular pressure (IOP), between 21 and 185 days (median 41 days). LSL was effective in decreasing the IOP to acceptable levels in 10 (66.6%) of the 15 eyes. No complications related to LSL were noticed. CONCLUSION: The reversibility of midterm failure seems to be a unique feature of trabeculectomies with MMC.

Corneal incision phacoemulsification and internal bleb revision.

BACKGROUND AND OBJECTIVE: Cataract extraction in filtered eyes often leads to decreased outflow and, eventually, to bleb failure. The authors describe a surgical technique that promotes preservation of the filtering bleb. PATIENTS AND METHODS: The authors retrospectively reviewed 19 eyes of 19 consecutive patients who underwent corneal incision phacoemulsification and simultaneous internal revision of the previous filtering bleb. RESULTS: The mean follow-up time was 13.6 +/- 7.6 months. Visual acuity improved in all patients (89.4 percent achieved 20/40 or better). No significant difference was noted between preoperative and postoperative intraocular pressures and astigmatism. The bleb was preserved in 89.4 percent of the eyes at the time of the last follow-up. CONCLUSIONS: This surgical technique proved to be safe and yielded good results.