Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia.
OBJECTIVE
To investigate the effects of timolol maleate with preservative and its preserved (PV) and nonpreserved vehicles (NPV) (benzalkonium chloride) on the blood-aqueous barrier and angiographic cystoid macular edema (CME) in early postoperative pseudophakia.


METHODS
Patients with ocular hypertension, normal tension glaucoma, and primary open-angle glaucoma who underwent surgery for cataracts. The study included a double-masked trial for timolol, PV, and NPV and a single-masked trial on the effect of diclofenac sodium and fluorometholone acetate on all three. The patients were divided into 6 groups, each of which were simultaneously administered the following different combinations of compounds: timolol and diclofenac (group A), timolol and fluorometholone (group B), PV and diclofenac (group C), PV and fluorometholone (group D), NPV and diclofenac (group E), and NPV and fluorometholone (group F). The 6 groups were then compared using a laser flare cell meter to determine the degree of disruption of the blood-aqueous barrier and fluorescein angiography to investigate angiographic CME. The differences in mean daily fluctuations in intraocular pressure were compared on the preoperative baseline day and for 5 weeks postoperatively. Twice daily administration of 0.5% timolol maleate or the vehicles was started 2 days before surgery, and continued until 5 weeks after surgery. Diclofenac or fluorometholone drops were instilled in the eyes 4 times preoperatively, on the day of surgery, and 3 times daily for 5 weeks postoperatively.


RESULTS
The flare amount was higher on the third and seventh days in group B than in group D, but was the same after the seventh day. The incidence of angiographic CME was the same between both groups. These 2 factors were significantly lower in group F. These 2 factors were also significantly lower in the 3 groups that received diclofenac instead of fluorometholone, with no difference among these groups. The intraocular pressure decline was significant in groups that received timolol compared with groups that received PV or NPV.


CONCLUSIONS
Timolol and its preservative, benzalkonium chloride, cause disruption of the blood-aqueous barrier in early postoperative pseudophakia and increased incidence of angiographic CME. The concurrent administration of nonsteroidal anti-inflammatory drug such as diclofenac prevents these adverse effects without interfering with the drop in intraocular pressure caused by timolol. The addition of benzalkonium chloride to timolol contributes considerably to these adverse effects.


CONCLUSIONS
The present results suggest the cause of similar complications produced by other antiglaucoma eyedrops containing similar preservatives.
Shohzankai Medical Foundation, Miyake Eye Hospital, 1070-Kami 5, Higashiozone-cho, Kita-ku, Nagoya, 462-0823, Japan. miyake@spice.or.jp
K
K
Miyake
I
I
Ota
N
N
Ibaraki
J
J
Akura
S
S
Ichihashi
Y
Y
Shibuya
K
K
Maekubo
S
S
Miyake
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000869:Anterior Eye Segment / Q000098:blood supply*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000009:adverse effects; D018916:Blood-Aqueous Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D004008:Diclofenac / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D005469:Fluorometholone / Q000627:therapeutic use; D005902:Glaucoma, Open-Angle / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007429:Intraocular Pressure / Q000187:drug effects; D008269:Macular Edema / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000009:adverse effects*; D019591:Pseudophakia / Q000150:complications* / Q000188:drug therapy; D016037:Single-Blind Method; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects*
D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001548:Benzalkonium Compounds; D011310:Preservatives, Pharmaceutical; D004008:Diclofenac; D013999:Timolol; D005469:Fluorometholone