Once an unpredictable foe lurking behind the microscope, endophthalmitis is now being challenged by smarter prevention strategies, molecular diagnostics and modern surgical finesse.
By all accounts, few words strike more fear into a vitreoretinal surgeon’s heart than endophthalmitis. This rare yet devastating infection of intraocular tissues remains one of the field’s most dreaded complications.
“The primary risk factors for endophthalmitis after cataract or vitreoretinal surgery include wound leak, posterior capsule violation, vitreous prolapse and prolonged surgical time,” said Dr. Landon Rohowetz (USA), a vitreoretinal surgeon at the Bascom Palmer Eye Institute.
“Identifying and addressing these complications intraoperatively significantly reduces the risk of developing endophthalmitis,” he added.
In other words, prevention begins before the first drop of povidone-iodine hits the ocular surface. From meticulous draping to managing pre-existing conditions, every detail counts in closing the door on endophthalmitis before it even knocks.
Sterile starts and smart prevention
When it comes to infection control, there’s nothing glamorous about sterile technique, but it remains the most powerful weapon in a vitreoretinal surgeon’s arsenal. “Preoperative preventive measures—including meticulous sterile technique and draping of the eye, preparation of the ocular surface with povidone-iodine and treatment of meibomian gland disease—are particularly important,” Dr. Rohowetz explained.
The pre-op checklist might sound old-school, but it is supported by decades of evidence.
Data from a large retrospective study of 68,323 intraocular surgeries conducted at a single center from 1990 to 2009 suggest that generous preoperative application of povidone–iodine may reduce the risk of endophthalmitis.1
The European Society of Cataract and Refractive Surgery (ESCRS) recommends using 5% to 10% povidone-iodine prior to cataract surgery, while the American Academy of Ophthalmology (AAO) recommends 5%.2 So, whether you’re in Barcelona or Boston, the message is: iodine works.
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Equally important is recognizing patients who walk in with preloaded risks. “Those with blepharitis, previous intraocular trauma, diabetes mellitus and other forms of immunosuppression” are especially vulnerable, Dr. Rohowetz noted. Proper preoperative management of these systemic and ocular conditions can make all the difference in keeping the postoperative course uneventful.
And what about the perennial debate surrounding prophylactic intracameral antibiotics? Opinions are divided. “The role of prophylactic intracameral antibiotics, while used in many parts of the world, is unclear,” Dr. Rohowetz said.
The landmark 2007 ESCRS trial demonstrated that intracameral cefuroxime could cut the risk of postoperative endophthalmitis.3 Yet, the findings have not achieved universal adoption, particularly in the United States, where variations in drug availability, regulatory approvals and workflow preferences continue to shape clinical decisions.
Diagnosing the invisible
Despite our technological advances, diagnosing endophthalmitis can still feel a bit like detective work in the dark. Traditional cultures—long considered the gold standard—fail to yield results in up to 70% of suspected cases.4 That leaves clinicians treating empirically and often guessing at the invisible culprit.
Enter molecular diagnostics, a 21st-century upgrade to an age-old problem. Techniques such as polymerase chain reaction (PCR) and next-generation sequencing (NGS) can identify pathogens more rapidly and in more cases than conventional cultures.5
These methods, Dr. Rohowetz said, have “expanded our ability to identify causative organisms in cases of culture-negative endophthalmitis.”
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However, these molecular marvels don’t come cheap. “A primary challenge to implementing these technologies is their associated costs, as most practices and small laboratories do not have the resources necessary to expend on these technologies,” he noted. As a result, they remain largely confined to major tertiary academic centers.
Even where resources abound, the jury’s still out on whether faster and broader microbial detection translates to better outcomes. “It is unclear if their capacity for microbiologic diagnosis impacts management strategies and treatment outcomes,” Dr. Rohowetz cautioned. Before they become routine, “these factors must be addressed.”
Still, as the technology matures and costs decline, it’s not hard to imagine a future where a PCR panel could become as routine as a slit-lamp exam.
Revisiting old playbooks
To understand how far we’ve come, it helps to recall how it all began. In the 1970s, when Dr. Gholam Peyman introduced the concept of intravitreal antibiotics in rabbit models, leading to the “tap and inject” era. Soon after, Dr. Robert Machemer and his colleagues pioneered pars plana vitrectomy (PPV), adding another powerful tool in the ophthalmic arsenal.
The Endophthalmitis Vitrectomy Study (EVS) of the late 1980s and early 1990s helped define the standard approach, finding no clear benefit of vitrectomy over intravitreal antibiotics for post-cataract cases, with visual acuity better than light perception. For decades, these guidelines served as gospel.
But medicine, like technology, doesn’t stand still. “In light of these advancements, some have expanded the role of PPV in the treatment of endophthalmitis,” said Dr. Rohowetz. With today’s small-gauge vitrectomy systems and modern phacoemulsification, what was once a high risk procedure has become faster, safer and more refined.
Modern decision-making is also more nuanced. “Some authors have instituted more nuanced approaches to decision-making, relying on a combination of objective measures including fundus visualization, corneal transparency and the presence of a hypopyon when determining the optimal initial management approach,” he explained.
Still, Dr. Rohowetz noted, “convincing evidence for either approach is limited and the decision to perform vitrectomy should take into account disease severity on presentation, response to initial intravitreal antibiotic therapy and suspected organism virulence.”
It seems the old “tap and inject” versus “cut and clear” debate still has a few rounds left to play out.
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New tools, new frontiers
Where does the field go from here? According to Dr. Rohowetz, “promising research directions include the development of advanced diagnostic techniques to allow the rapid identification of organisms to potentially enable more targeted therapeutic approaches, expansion of the role of intracameral antibiotics and sustained release antimicrobial materials, and continued refinement of vitreoretinal and cataract surgery techniques.”
One particularly exciting avenue lies in novel drug delivery systems. Innovations such as drug-eluting intraocular lenses, hydrogels and nanoparticles are being engineered to overcome the eye’s formidable barriers: corneal, conjunctival and blood-ocular alike. These systems could prolong drug residence time, improve permeability and solubility, and reduce toxicity, paving the way for more effective and sustained prophylaxis.5
The bigger picture
For a condition that occurs in only 0.03% to 0.7% of surgeries, endophthalmitis casts a long shadow.6 Each case is a stark reminder that even in the era of femtosecond lasers and micro-incisions, infection remains a formidable adversary. Delays in diagnosis or treatment can mean permanent vision loss, underscoring why vigilance and innovation must go hand in hand.
The next decade will likely redefine what infection control means in ophthalmology, shifting from a reactive approach to a predictive, precision-guided model. With molecular tools illuminating the unseen, smarter prophylactic strategies taking root, and surgical advances continuing apace, the fight against endophthalmitis is moving beyond the microscope…and perhaps, finally, beyond fear.
Editor’s Note: This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore. A version of this article was first published in PIE Issue 37.
References
- Gess AJ. Support for generous iodine use to reduce postop endophthalmitis risk. American Academy of Ophthalmology. February 18, 2015. Available at: https://www.aao.org/education/editors-choice/povidone-iodone-may-be-key-to-decreasing-postop-en. Accessed on October 26, 2025.
- Garcia O’Farrill N, Abi Karam M, Villegas VM, et al. New approaches to overcoming antimicrobial resistance in endophthalmitis. Pharmaceuticals. 2024;17(3):321.
- Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: Preliminary report of principal results from a European multicenter study. J Cataract Refract Surg. 2006;32(3):407-410.
- Naik P, Gandhi J, Joseph J. Recent advances and ongoing challenges in the diagnosis of culture negative endophthalmitis. Semin Ophthalmol. 2022;38(1):92-98.
- Mahaling B, Baruah N, Dinabandhu A. Drug delivery systems for infectious eye diseases: Advancements and prospects. Journal of Nanotheranostics. 2024;5(4):133-166.
- Harley O, Amelia YS, Gustianty E, et al. Controversies in the management of endophthalmitis: A 5-year retrospective cohort study. J Ophthalmic Inflamm Infect. 2025;15(1):28.
