A Comparative Analysis Of Corneal Surgical Outcomes Across Different Populations Of Neurotrophic Keratitis Patients

Neurotrophic keratitis (NK) is a degenerative corneal disorder resulting from damage to the ophthalmic division of the trigeminal nerve, which can lead to non-healing epithelial defects and neurotrophic corneal ulcers. While Herpes Simplex Virus (HSV), Herpes Zoster Ophthalmicus (HZO), prior refractive surgery, and Diabetes Mellitus (DM) are among the most common causes of NK, few studies compare treatment approaches and surgical outcomes across these distinct etiologies. This is an epidemiologic study examining the rates of amniotic transplants, tarsorrhaphy, and penetrating keratoplasty (PK) among patients with HSV, HZO, post-refractive surgery, and DM.

This study uses data from the TriNetX Global Collaborative Network procured according to the associated ICD-10 codes for HSV, HZO, prior refractive surgery, and DM diagnoses, as well as CPT codes for procedures, including amniotic transplants, tarsorrhaphy, and penetrating keratoplasty (PK). 

Using data from the TriNetX Global Collaborative Network procured according to the associated CPT and ICD-10 codes, we conducted a retrospective cohort study of NK patients (n=9,700) stratified by HSV (n=1,755), HZO (n=1,118), refractive surgery (n=1,432), and diabetes (n=2,785). The populations were propensity score-matched for age, gender, race, and ethnicity. The primary outcome assessed was the prevalence of amniotic membrane grafts for epithelial defects in NK patients in each cohort, relative to the HSV subset, with secondary outcomes examining patients with corneal ulcers who underwent more escalated measures, such as tarsorrhaphy and penetrating keratoplasty.

Kaplan-Meier analysis did not show significant hazard ratios for amniotic membrane transplant across all four cohorts: HSV vs. HZO, HSV vs. refractive, and HSV vs. DM, with p-values >0.05. Secondary outcomes showed a significant difference in the prevalence of corneal ulcers only in the HSV vs. refractive groups (n_HSV=107, n_refract=90; p=0.0073). Tarsorrhaphy results were not significant across all groups: HSV vs. HZO, HSV vs. refractive, and HSV vs. DM, with p-values >0.05. However, the prevalence of PK was significantly lower in post-refractive (n_HSV=109, n_refract=52, p=0.002) and DM patients compared to HSV patients with NK (n_HSV=126, n_DM=127; p=0.003), with no significant difference between HSV and HZO patients (n_HSV=77, n_HZO=69).

Patients with HSV, VZV, and post-refractive surgery-associated neurotrophic keratitis hold similar rates across amniotic membrane graft and tarsorrhaphy interventions to encourage corneal healing. Refractive patients had significantly fewer corneal ulcer complications. However, the decreased risk of penetrating keratoplasty among post-refractive and DM cohorts suggests an increased burden of neutrophilic corneal disease in HSV- and VZV-associated NK. As treatments such as corneal neurotization become more available, it is important to understand the current interventions for different populations of NK.