Monthly Note: Eye Drops

Prednisolone is a steroid eye drop routinely offered to patients undergoing different kinds of eye surgeries around the world. A few weeks ago, the US Food and Drug Administration (FDA) reported that an Indian manufacturer had issued a voluntary recall for over 2.5 million prednisolone eye drop bottles sold in the United States. Earlier, in June, the All India Ophthalmological Society (AIOS) had issued a critical safety alert concerning multiple batches of an eye drop found contaminated with Pseudomonas bacteria, following which the affected batches were recalled.

These incidents bring back memories of a serious outbreak in the United States in 2023, when contaminated artificial tear drops were linked to infections caused by drug-resistant strains of Pseudomonas aeruginosa. The outbreak resulted in loss of vision and tragically, some deaths—one of the worst reported instances of this kind. The source of those contaminated eye drops too turned out to be an Indian pharmaceutical company.

There is, however, an important difference between the two time-periods: unlike in 2023, in the recent prednisolone episode there have been no reports of harm, and the manufacturing company voluntarily notified the US FDA and recalled the product. We are yet to understand the full impact of the AIOS critical safety alert issued in June.

These may be unrelated events, but together they remind us of something fundamental: when a medicine is placed in the eye, an enormous amount of trust accompanies every single drop.

The ocular microbiome

As eye-care professionals, we have the privilege of working with a delicate organ. The eye maintains a finely balanced environment protecting its tissues while defending itself against injury and pathogens to which it is constantly exposed. The ocular surface is also home to its own community of microorganisms–the ocular microbiome. The late Shivaji Sisinthy, who headed our Research function, had dedicated the latter part of his career to understanding and characterising this fascinating ecosystem.

Contaminated eye drops can bypass many of the body’s natural defences, including the natural microbiome, and introduce pathogens directly onto the ocular surface. This is particularly relevant for people who have recently undergone eye surgery, or people with dry eye diseases, or those who wear contact lenses. They may have small disruptions on their ocular surface, which can provide an opportunity for pathogens to gain a foothold. The consequences are much more serious when the contaminating organism is resistant to antibiotics.

This is a real danger–we live in a world where antimicrobial resistance (AMR) to drugs is growing. At LVPEI, Joveeta Joseph, who heads the Jhaveri Microbiology centre, has been tracking and monitoring antimicrobial resistance across our hospital network. Using modern genetic tools, including whole genome sequencing, her team working with colleagues at the Centre for Cellular and Molecular Biology (CCMB) are able to sequence bacterial samples from our clinics and not only identify the set of genes that bestow resistance, but also monitor emerging novel genetic changes in these microorganisms.

In April this year, the group analysed 291 bacterial genomes using long-read sequencing of isolates obtained from eye infection cases managed at our Kallam Anji Reddy campus and uncovered critical insights into drug resistance. Nearly 45% of the isolates were multidrug-resistant (MDR), showing resistance to multiple classes of antibiotics while more than 15% were extensively drug-resistant (XDR), severely limiting viable treatment alternatives. Their work also discovered a few previously unknown drug resistant mechanisms and bacterial lineages.

Such discoveries reinforce why surveillance cannot be an occasional exercise. Microorganisms continue to evolve, and our ability to treat infection must evolve with them.

The eye drops landscape

At LVPEI, our interest in this issue extends beyond treating infections or monitoring antimicrobial resistance.

We are pushing the boundaries of pharmaceutical, serological, cellular, and bio-engineered products for the eye—all to a quality that meets strict standards of manufacture. At the Kallam Anji Reddy campus, we have a research-scale Good Manufacturing Practice (GMP) facility supporting this work. Our colleagues also contribute to broader discussions around ophthalmic policy, regulations and development of supply chains that can consistently deliver safe and effective products.

The scale at which eye drops are used makes vigilance particularly important. The pharmacy at our Kallam Anji Reddy campus alone dispenses over 250,000 eye drop bottles, on average, every month while the campus’ internal consumption exceeds 100,000 bottles every year. 

Numbers of this magnitude make surveillance a clinical responsibility.

Our teams therefore closely monitor patterns in eye infection cases and the microorganisms causing them. When an unusual pattern appears, possible sources including eye drops, irrigating fluids, devices and contact lenses are brought to investigation. The ability of clinicians, microbiologists, pharmacists and quality teams to connect these signals quickly is an important strength of an integrated eye-care institution. 

What needs to be done

No manufacturing or healthcare system can assume that an adverse event will never occur. What distinguishes a strong system is how quickly it detects a problem, how transparently it communicates it, and how decisively it responds. Voluntary recalls, practitioner-manufacturer feedback mechanisms, active regulatory agencies—are all signs of a system that worked in Prednisolone eye drop recall this year.

High-quality, uncompromising Good Manufacturing Practice must be the baseline.  Medicines should meet the same high standards irrespective of the market for which they are produced. But even with stringent standards, millions of bottles travel through complex supply chains, across different climates and geographies. Further, many eye drops are prepared without preservatives, although with good intentions, putting them at a higher risk of contamination. Vigilance, therefore, cannot end at the factory gate.

Clinicians and clinical facilities play a critical role in this safety system. An alert ophthalmologist may be the first person to notice an unusual cluster of infections. Microbiologists identify similarity in microorganisms pointing to a common source. Pharmacists and quality teams trace products and batches. Professional societies rapidly alert their members. Manufacturers investigate and recall products when necessary. Regulatory agencies connect reports across institutions and geographies and take coordinated action.

Each stakeholder is important and none can work effectively in isolation.

At the centre of this entire system is the patient; the person who places a drop in the eye trusting that everyone involved in developing, manufacturing, prescribing, dispensing and regulating that medicine has done their job well. They trust us to act in good-faith, and to step in to do our best when circumstances turn sour. This trust places a special responsibility on all of us.

At LVPEI, we take this responsibility seriously. Every day, we observe patterns of diseases, identify emerging organisms, monitor resistance to our frontline drugs and occasionally encounter an event that does not fit the expected pattern. Recognising those signals, asking the right questions, and acting quickly help prevent an isolated event from becoming an outbreak.

We remain vigilant.