Ocular Surface Microbiome Profiling In Patients With Neurodegenerative Disorders

Neurodegenerative disorders (NDD), especially Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive neuronal loss, chronic systemic inflammation, autonomic dysfunction, and sensory impairment. These multidimensional changes directly affect the ocular surface, contributing to development of dry eye disease (DED) and possible microbial dysbiosis at the ocular surface. We aimed to characterize the ocular surface microbiome and ocular surface parameters in patients with NDDs and compare them to healthy controls.

A prospective cross-sectional study was undertaken from March 2024 to September 2025 in the Ophthalmology and Neurology department, All India Institute of Medical Sciences, New Delhi, India and Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India to recruit willing participants with Alzheimer’s and Parkinson’s disease. An equal number of age and gender matched controls with no ocular or systemic disease were also recruited. 

Systemic workup including stage of disease was noted. All patients underwent thorough ophthalmic evaluation, non-invasive Ocular Surface Analyzer (OSA)-based DED assessment [Non-invasive Break up Time (NIBUT), Tear Meniscus Height (TMH), Lipid Layer Thickness (LLT), Meibomian Gland Loss (MGL) and Ocular Surface Disease Index (OSDI) assessment. Conjunctival swab samples were collected from all study participants for microbiome analysis. Ocular surface microbiome analysis was done using whole genome metagenomic sequencing (Nanopore and/or Illumina platforms). Relative abundances of microbial flora were compared between the patient groups and controls.

59 subjects were enrolled: 20 PD, 19 AD, and 20 controls. DED prevalence was high in AD (93%) and PD (90%) patients. Alpha diversity was significantly higher in AD and PD groups compared with controls, indicating increased species richness and microbial heterogeneity. Disease groups demonstrated loss of commensal dominance (Corynebacterium, Staphylococcus epidermidis) and increased representation of gut-associated and environmental species (Segatella copri, Enterobacter cloacae in AD Pseudomonas aeruginosa, Kocuria palustris in PD). Patients with DED exhibited greater dysbiosis, notably Segatella overrepresentation, compared to NDD patients without DED.

Patients with Neurodegenerative disorders exhibit pronounced DED, accompanied by distinct microbial dysbiosis. Our study showed that the ocular surface microbiome was distinctly altered in NDD patients, such as AD and PD, compared to healthy controls, with higher microbial diversity and increased species richness, indicative of a significant distortion from the normal ocular microbial flora. Ocular surface microbiome alterations may serve as a potential biomarker reflecting underlying neuroinflammation and autonomic dysfunction in neurodegenerative disease. Whole-genome metagenomics provides a powerful tool for identifying these dysbiotic signatures.