Phase II results of an intraocular steroid delivery system for cataract surgery

doi:10.1016/S0161-6420(99)90262-2

Ophthalmology

Volume 106, Issue 6, 1 June 1999, Pages 1172-1177

Presented in part at the American Academy of Ophthalmology annual meeting, New Orleans, Louisiana, November 1998.

https://doi.org/10.1016/S0161-6420(99)90262-2 Get rights and content

Abstract

Objective

To evaluate the safety and efficacy of an intraocular biodegradable polymer dexamethasone drug delivery system (DEX DDS) in treating postoperative inflammation after cataract surgery.

Study design

Multicenter, randomized, double-masked, parallel group study comparing two dose levels of the DEX DDS to concurrent placebo and no treatment control subjects.

Participants

Ninety patients scheduled to undergo extracapsular cataract extraction with phacoemulsification and intraocular lens implantation participated in the study.

Intervention

One or two DEX DDSs, each containing 60 μg of dexamethasone, were placed in the posterior chamber after cataract surgery. Patients receiving the placebo received a DDS composed of the same matrix with no active drug. In vivo rabbit studies have determined that the DEX DDS releases dexamethasone into the anterior chamber (AC) for approximately 7 to 10 days.

Main outcome measures

The AC cells and the AC flare were assessed over a 60-day postoperative period using slit-lamp examination by masked observers. The number and percent of patients in each treatment group requiring additional postoperative topical anti-inflammatory medication were compared.

Results

Ninety patients were randomized into 4 treatment groups (30 to the 2 DEX DDS group, 30 to the 1 DEX DDS group, 15 to the placebo DDS group, and 15 to the no treatment group). The control patients required the addition of topical steroids as rescue medication more frequently and sooner than patients receiving DEX DDS (80% vs. 7% at week 2) (P < 0.001). Patients receiving DEX DDS showed a significant reduction in postoperative inflammation as assessed by the combined AC cell and flare scores when compared to the control group from day 3 (P = 0.002) through week 3. The DEX DDS was well tolerated. No clinically significant difference in any safety evaluations, including intraocular pressure, was seen between the DEX DDS-treated and control groups.

Conclusion

The DEX DDS was safe and effective in suppressing postoperative inflammation after uncomplicated cataract surgery. Additional topical anti-inflammatory drops were not needed for most patients.

Section snippets

Patients and methods

The DEX DDS is a white/off-white rod-shaped filament approximately 0.5 mm in diameter and 1.0 mm in length composed of dexamethasone in a biodegradable polymer matrix. It contains nominally 60 μg of dexamethasone (United States Pharmacopeia). The placebo DDS is identical to the DEX DDS in both appearance and composition of the matrix but contains no dexamethasone.

The protocol and informed consent forms were approved by the Institutional Review Board at each investigational site, and a written

Results

Ninety patients requiring cataract surgery were randomized in a 2-to-1 ratio into active or control treatment groups at 4 study centers. Thirty patients were assigned to receive 2 DEX DDSs, 30 were assigned to receive 1 DEX DDS, 15 were assigned to receive a placebo DDS, and 15 were assigned to receive no treatment. One patient assigned to receive one DEX DDS actually received no treatment, while another patient assigned to receive a placebo DDS actually received two DEX DDSs. Eighty-nine

Discussion

Although steroids are widely used in the treatment of postoperative inflammation after cataract surgery, there are few studies in the literature documenting the efficacy of this treatment. When this study was initiated, rimexolone (Vexol, Alcon) was the only steroid that had been proved efficacious over placebo by a randomized, prospective study and approved by the United States Food and Drug Administration for the treatment of postoperative inflammation.9, 10 For this reason, the DEX DDS was

References (16)

D.J Apple et al.
Posterior capsule opacification
Surv Ophthalmol
(1992)
M.A Kass et al.
Compliance with topical pilocarpine treatment
Am J Ophthalmol
(1986)
K.K Assil et al.
Control of ocular inflammation after cataract extraction with rimexolone 1% ophthalmic suspension
J Cataract Refract Surg
(1997)
D.T.H Tan et al.
Randomized clinical trial of a new dexamethasone delivery system (Surodex™) for treatment of post-cataract surgery inflammation
Ophthalmology
(1999)
I.H Leopold
Nonsteroidal and steroidal anti-inflammatory agents
J.L Tennant
Cystoid maculopathyprostaglandins in ophthalmology
D.R Sanders et al.
Steroidal and nonsteroidal anti-inflammatory agents. Effect on postsurgical inflammation and blood-aqueous humor barrier breakdown
Arch Ophthalmol
(1984)
V.M.G Ferguson et al.
Recovery of the blood-aqueous barrier after cataract surgery
Br J Ophthalmol
(1991)

There are more references available in the full text version of this article.

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Prospective, noncomparative clinical study.
A cohort of patients who underwent cataract extraction surgery had several eyelashes removed preoperatively that were examined independently by the hospital laboratory for the presence of the Demodex mite. This was repeated 3 weeks after surgery. During several postoperative weeks, patients received the standard treatment of steroid drops alone for a period as individually required.
A total of 62 patients were included in the study (31 men and 31 women), with a mean age of 71.04 years (range, 47-87). In the group positive for Demodex, the male-to-female ratio was 2:3 (P = .2772). Demodex colonization was observed in 22.58% of samples before cataract surgery and in 32.26% after cataract surgery and topical postoperative steroid therapy (P = .0143).
There is a statistically significant increase in Demodex colonization of eyelashes after cataract surgery and postoperative topical steroid treatment. Although Demodex colonization does not necessarily cause blepharitis, our findings of increased colonization should raise the possibility of Demodex blepharitis being considered by ophthalmologists in patients with chronic postoperative eye discomfort after cataract surgery. This study was carried out at the Emek Medical Center.
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Citation Excerpt :
Between postoperative 4 days and 45 days, 3.5-fold to 6.5-fold fewer sustained-release dexamethasone patients than placebo patients required rescue medications. These results corroborate those of Chang et al.,24 who reported that fewer patients receiving dexamethasone required rescue medications than their counterparts on placebo. Through 30 days, the proportion of patients requiring rescue medications was less than 21% in the sustained-release dexamethasone group, indicating that the masked investigators judged that the dexamethasone alone was providing adequate control of postoperative inflammation in most cases.
To evaluate the safety and efficacy of dexamethasone as a sustained-release drug depot when placed in the canaliculus for the treatment of ocular inflammation and pain in cataract surgery patients.
Four private practice sites in the United States.
Multicenter randomized double-masked clinical trial.
Patients were randomized (1:1) to receive either the sustained-release dexamethasone or a placebo vehicle punctum plug inserted into the inferior distal canaliculus of the operated eye intraoperatively during cataract surgery. The primary endpoints were the proportions of patients with absence of cells or pain in the anterior chamber at 8 days. Secondary endpoints included cells, flare, pain, and the presence of the device at various timepoints through 30 days.
Approximately one fifth (20.7%) of patients in the sustained-release dexamethasone group had an absence of anterior chamber cells at 8 days compared with 10.0% in the placebo group (P = .1495). A higher proportion of patients in the sustained-release dexamethasone group (79.3%) than in the placebo group (30.0%) had an absence of ocular pain at 8 days (P < .0001) and at all other timepoints (P < .0002). There were significantly higher proportions of patients in the sustained-release dexamethasone group than in the placebo group with an absence of anterior chamber cells, anterior chamber flare, and pain at several timepoints through 30 days (P ≤ .0251).
Sustained-release dexamethasone provided elution of drug for up to 1 month after cataract surgery, providing clinically significant reductions in inflammation and pain.
Dr. Masket is a consultant to and shareholder in Ocular Therapeutix, Inc. No other author has a financial or proprietary interest in any material or method mentioned.
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Even the newer, less potent corticosteroids may elevate IOP.1,83,84,192 It remains to be seen whether the newer corticosteroid delivery systems will overcome some of these toxicities.52,313 Corticosteroids have been compared to topical NSAIDs in an effort to establish their relative toxicities.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly employed in ophthalmology to reduce miosis and inflammation, manage scleritis, and prevent and treat cystoid macular edema associated with cataract surgery. In addition, they may decrease postoperative pain and photophobia associated with refractive surgery and may reduce the itching associated with allergic conjunctivitis. In recent years, the U.S. Food and Drug Administration has approved new topical NSAIDs, and previously approved NSAIDs have been reformulated. These additions and changes result in different pharmacokinetics and dosing intervals, which may offer therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on NSAIDs and a summary of their current uses in ophthalmology with attention to potential future applications.
A biodegradable drug delivery system for the treatment of postoperative inflammation
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Cataract surgery is often performed in patients suffering from associated pathologies. Our goal is to develop a biodegradable drug delivery system (DDS) combined with the artificial intraocular lens (IOL). DDS were manufactured using poly(d,l-lactide-co-glycolide), or PLGA, and were loaded with triamcinolone acetonide (TA). The loading capacity was approximately 1050 μg of TA per DDS. The higher the molecular weight of PLGA (34,000, 48,000 and 80,000 Da), the slower was the release of TA in vitro. Cataract surgery was performed on the right eye of rabbits. IOL was inserted with (i) no DDS, (ii) unloaded DDS PLGA48000, (iii) one loaded DDS PLGA48000, (iv) two loaded DDS. The number of inflammatory cells and the protein concentration were measured in the aqueous humor (AH). Unloaded DDS showed good ocular biocompatibility. One DDS PLGA48000 loaded with TA significantly reduced postoperative ocular inflammation. Two loaded DDS PLGA48000 was even more effective in inhibiting such inflammation. On long-term observation (days 63 and 84), reduction of inflammation could be obtained by insertion of one DDS PLGA48000 and a second DDS PLGA80000. Therefore, our “all in one” system is very promising since it could replace oral treatment and reduce the number of intraocular injections.
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^☆: Supported by Oculex Pharmaceuticals, Inc., Sunnyvale, California.

¹: Dr. Hunkeler is an investor in Oculex Pharmaceuticals, Inc., and has received contract payments for research. None of the other authors has a proprietary interest in Oculex Pharmaceuticals or in the product discussed in this article.

View full text

Phase II results of an intraocular steroid delivery system for cataract surgery☆

Abstract

Objective

Study design

Participants

Intervention

Main outcome measures

Results

Conclusion

Section snippets

Patients and methods

Results

Discussion

Surv Ophthalmol

Am J Ophthalmol

J Cataract Refract Surg

Ophthalmology

Nonsteroidal and steroidal anti-inflammatory agents

Cystoid maculopathyprostaglandins in ophthalmology

Steroidal and nonsteroidal anti-inflammatory agents. Effect on postsurgical inflammation and blood-aqueous humor barrier breakdown

Arch Ophthalmol

Recovery of the blood-aqueous barrier after cataract surgery

Br J Ophthalmol