Serial Anti-VEGF Injections May Benefit the Ocular Surface in nAMD Eyes


Repeated injections with preoperative povidone-iodine application was associated with reduced meibomian gland loss, increased tear volume, and reduced signs of inflammation.

Serial intravitreal injections (IVI) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD) may have a beneficial effect on the ocular surface, according to new research.

The findings suggest repeated IVI with anti-VEGF with preoperative povidone-iodine application was associated with reduced meibomian gland loss, increased tear volume, and reduced signs of inflammation compared to fellow non-treated eyes.

“Contrary to our hypothesis that repeated IVI injections increases the risk of dry eye disease, our study revealed healthier values of various dry eye parameters in eyes treated with IVI compared to the fellow untreated eyes,” wrote corresponding author Agni Malmin, MD, Department of Ophthalmology, Stavanger University Hospital. “This raises the question: Can repeated IVI have a positive effect on the ocular surface, and in such case, what are the mechanisms?”

Anti-VEGF injections have notable effects on visual acuity and drug tolerance but must be repeated continuously for months to years due to the natural course of macular diseases. Procedural complications, including sterile and infectious endophthalmitis, are widely reported, but studies on long-term surface effects of repeated injections remain limited.

Investigators cited issues of serial IVI, such as the toxic effect of pre-injection antisepsis of the ocular surface with povidone-iodine (polyvinylpyrrolidone-iodine, PVP-I) on the corneal epithelium and the predisposition of nAMD eyes to dry eye disease (DED). Their aim was to investigate the effect of serial IVI on the ocular surface and meibomian glands in nAMD patients treated with anti-VEGF.

Individuals with nAMD receiving unilateral IVI at the Department of Ophthalmology, Stavanger University Hospital were recruited to participate in the study. The inclusion criteria were at least two previous IVIs in a single eye, ongoing treatment intervals between 4-14 weeks, and at least a four-week interval between the last IVI and ocular surface assessments.

Ocular surface assessments were performed from least to most invasive, in order to minimize the impact on subsequent measurements. Tear meniscus height (TMH), non-invasive tear film break-up time (NIBUT), and bulbar redness score (BR) were measured, as was tear film osmolarity (TOsm). Corneal staining was assessed using a biomicroscope with cobalt filtered light and fluorescein tear film break-up time (TBUT) was recorded as the time interval between a complete blink and the first emergence of a dry spot in the precorneal tear film.

Meibomian gland expressibility (ME) was evaluated based on the number of expressible meibomian glands among the central five glands using a four-point score (0: 5 glands expressible; 1: 3–4 glands expressible; 2: 1-2 gland expressible; 3: 0 glands expressible). Meibum quality (MQ) of each gland was assessed according to a four-point score (0: clear; 1: cloudy; 2: granular; 3: toothpaste) and a sum and average score for the eight central glands was calculated (sum score range 0 – 24).

A total of 90 patients with a mean age of 77.5 years were included, 47 of which were male (52%). Data show the median number of IVI in treated eyes was 19.5, while the median number of IVI received during the last 12 months was 8 and the median time intervals between the most recent IVI was 4 weeks.

Meibography images of both lower eyelids were of sufficient quality for interpretation in 79 (88%) patients, and for the upper lid in 33 (37%) patients. The mean MG loss in the upper eyelid was 19.1% in treated eyes and 25.5% in untreated fellow eyes (P = .001).

Meanwhile, for the lower eyelid, the median MG loss was 17.4% in treated eyes and 24.5% in fellow eyes (P <.001). Data show the mean bulbar redness score was 1.32 in treated eyes versus 1.44 in fellow eyes (P = .017) and the median TMH was 0.36 mm in treated eyes and 0.32 mm in fellow eyes (P = .02).

Investigators noted there were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, ME, or MQ.

“Further investigations with prospective studies are warranted to support our findings and explore the mechanisms involved,” Malmin wrote.

The study, “Associations between serial intravitreal injections and dry eye,” was published in Ophthalmology.

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