SAFETY PROFILE OF OCRIPLASMIN FOR SYMPTOMATIC VITREOMACULAR ADHESION: A Comprehensive Analysis of Premarketing and Postmarketing Experiences.

PURPOSE: After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. METHODS: Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. RESULTS: Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. CONCLUSION: Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.

Effects of alpha chymotrypsin on the canine eye.

Injection of 150, 500, or 750 U of alpha chymotrypsin into the posterior chamber of clinically normal Beagles resulted in changes in intraocular pressure and iridocyclitis. In the 6 eyes treated with 500 or 750 U, lens subluxation occurred in 4 eyes, retinal detachment in 1 eye, retinal degeneration in 1 eye, and optic nerve degeneration in 6 eyes. Scanning electron microscopic changes included dose-related zonulolysis and zonulary remnants within the aqueous humor outflow pathways. Ultrastructural changes by transmission microscopy of the optic nerve degeneration revealed loss of axoplasm and organelles and disruption of the myelin sheaths. Retinal and optic nerve changes may represent the direct toxic effects of alpha chymotrypsin and/or the indirect effects of increased intraocular pressure.

[Morphological changes in failure of the lenticular ligamentous-capsular system]. / Morfologicheskie izmeneniia pri nesostoiatel'nosti sviazochno-kapsuliarnogo apparata khrustalika.

Morphological changes in case of failure of the lenticular ligamentous-capsular system are described. Histological changes in this complex led the authors to the conclusion that morphological substrata of the "traumatic" and "surgical" lenticular subluxation are similar and are characterized by coarse mechanical changes in the lens capsule, with the relatively intact structure of the ligamentous system at a considerable length. Subluxation of the lens resultant from oral drug therapy is characterized by pronounced changes in the lens capsule and in the short cinnous ligament fibers. Age-associated or involution subluxation is caused primarily by pathological changes in the lens capsule, which seems to experience high strain from the remaining zonular fibers.

Complications of intraocular lenses in children.

Complications in a group of 91 children with congenital and traumatic cataracts in whom intraocular lenses (IOL) have been implanted have been studied. The influence of viscoelastic substances (Healon) in the prevention and treatment of some of these complications, and as a causal factor in others, is presented. Ten different styles of lenses were implanted allowing a comparison of the relationship between the type of lens fixation and the complications observed.

Dislocation of cataractous lens by enzymatic zonulolysis: a suggested solution to the problem of the 18 million individuals blind from cataracts in Third-World countries.

There are 18 million persons blind from cataracts in Third-World countries and the number is doubling every 20 to 25 years. It is impossible to cure this many blind with present sophisticated surgical techniques. Enzymatic dislocation of the cataractous lens could be performed by nonmedical personnel and the patients given inexpensive mass-produced spectacles, which could solve this tremendous problem.

Effect of succinylcholine on the intraocular contents of open globes.

The use of succinylcholine in patients with suspected or proven open globes is considered dangerous by some for fear of extruding the intra-ocular contents as a consequence of the co-contraction of the extraocular muscles it produces. To test this hypothesis, the authors devised an anterior and a posterior trauma model in the cat eye. Thirty events were studied using the anterior trauma model and eight with the posterior model. The only observable effect of succinylcholine administration was forward displacement of the lens and iris. No intraocular content was lost in any event. The authors believe this study supports the argument that, when indicated, succinylcholine may be considered in open globes.