In a recent column, I discussed neurotrophic keratitis (NK) induced by retinal injections in terms of related studies, and managing such patients (See "Dry Eye: Supporting Patients..."). Given that these injections are becoming ubiquitous treatments for age-related macular degeneration and diabetic macular edema, this month’s column focuses on the action steps we can take to detect early signs of NK in these patients.    

Obtain Injection and Risk Factor History 

When a patient reports receiving intravitreal injections, it is important to find out how many injections the patient has had and what type. This is because studies show a change in corneal nerve length and density after the third intravitreal injection.¹ Also, anti-vascular endothelial growth factor (anti-VEGF) injections can cause more damage to the corneas than other intravitreal injections because VEGF plays a healing role in accelerating regeneration of injured corneal nerves.² 

Additionally, inquire about the presence of risk factors for developing NK, including comorbidities. To review, a history of diabetes,^3,4 stroke, autoimmune disease, a previous diagnosis of dry eye disease, and a history of multiple ocular surgeries or corneal refractive surgery could increase the risk of developing NK.⁵ 

Provide a Symptom Survey 

I recommend using the Ocular Surface Disease Index survey, because several of its 12 questions pertain to vision. This is significant because, often, NK patients notice a reduction in clarity of vision before a change in ocular comfort. 

Assess Corneal Sensation 

Use a Cochet-Bonnet esthesiometer, a Brill esthesiometer, a cotton wisp, or unwaxed dental floss to accomplish this. A caveat: Do not instill eye drops in the patient’s eyes before evaluating corneal sensitivity. This is because they can affect corneal sensitivity, resulting in false results. Should you opt for a cotton wisp or unwaxed dental floss, Dr. Mark Milner, a Florida-based ophthalmologist and corneal specialist, developed a grading scale (see sidebar). “You want a quantitative measurement that you can use to compare in the future,” he has said.⁶ 

Employ Vital Dye Staining 

NK tends to have a corneal fluorescein staining pattern that involves the central cornea. The punctate epithelial defects (PED) found in stage 2 NK appear as smooth and rolled edges commonly located paracentral in the superior half of the cornea, due to impaired healing.⁷

Stage 3 NK is the most severe form and is characterized by central corneal ulcers and stromal involvement with thinning or melting. This stage requires urgent medical attention to prevent vision loss.⁸ 

Evaluate the Cornea and Conjunctiva 

In early NK, mild conjunctival hyperemia may be present. Also, the cornea will show epithelial irregularity, stromal haze, punctate keratopathy, superficial vascularization, and stromal scarring via slit lamp exam.⁹ I recommend showing this to patients taking intravitreal injections, so they understand the importance of follow-up appointments based on patient history.¹⁰  

A Call to Action 

NK is a progressive disease that becomes more difficult to treat as the disease advances. Therefore, identifying affected patients early presents an opportunity for intervention, which could ultimately halt the progression to end-stage NK and potential vision loss.¹¹ Let’s screen our intravitreal injection patients for NK on a regular basis, so we increase their likelihood of better outcomes. OM

References

1. Qi Y, Cui L, Zhang L, et al. Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves. Medicine (Baltimore). 2023;102(29):e34210. doi:10.1097/MD.0000000000034210

2. Brash JT, Denti L, Ruhrberg C, Bucher F. VEGF188 promotes corneal reinnervation after injury. JCI Insight. 2019;4(21):e130979. doi:10.1172/jci.insight.130979

3. Polat OA, Şener H, Erkiliç K. Corneal nerve fiber and sensitivity loss after repeated intravitreal anti-VEGF injections: an in vivo confocal microscopy study. Cornea. 2022;41(3):317-321. doi:10.1097/ICO.0000000000002836

4. Achtsidis V, Eleftheriadou I, Kozanidou E, et al. Dry eye syndrome in subjects with diabetes and association with neuropathy. Diabetes Care. 2014;37(10):e210-e211. doi:10.2337/dc14-0860

5. NaPier E, Camacho M, McDevitt TF, Sweeney AR. Neurotrophic keratopathy: current challenges and future prospects. Ann Med. 2022;54(1):666-673. doi:10.1080/07853890.2022.2045035

6. Feulner L, Ayers B, Milner M. Early testing for neurotrophic keratitis. Ophthalmology Management. October 27, 2025. Accessed January 20, 2026. https://ophthalmologymanagement.com/issues/2025/october/aao3/

7. Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, et al. Neurotrophic keratopathy: General features and new therapies. Surv Ophthalmol. 2024;69(5):789-804. doi:10.1016/j.survophthal.2024.04.004

8. Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989-995. doi:10.1038/sj.eye.6700616

9. Charters L. Neurotrophic keratopathy: finding different treatments. Ophthalmology Times. January 17, 2020. Accessed January 20, 2026. https://www.ophthalmologytimes.com/view/neurotrophic-keratopathy-finding-different-treatments

11. Avery RL, Bakri SJ, Blumenkranz MS, et al. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014;34 Suppl 12:S1-S18. doi:10.1097/IAE.0000000000000399
12. Singer M, O’Brien P, Mein L, Olvera A. Corneal sensitivity is inversely correlated with severity of diabetic retinopathy in a predominantly underrepresented population. Am J Ophthalmol. 2024;259:53-61. doi:10.1016/j.ajo.2023.08.010.

Pamela E. Theriot, OD, is the clinical director of the Dry Eye Relief Center at Lusk Eye Specialists, a multispecialty practice in Shreveport, Louisiana. In 2021, she was appointed to the public awareness committee of the Tear Film and Ocular Surface Society. In January 2025, she gave a TEDx Talk titled “Seeing Clearly in a Screen-Filled World: 3 Tips to Preserve Your Vision.”