Carreno-Galeano JT, Dohlman TH, Yin J, Dana R.
Limbal Stem Cell Deficiency Associated With Herpes Keratitis. Cornea 2021;40(8):967-971.
AbstractPURPOSE: To describe the demographic features and clinical characteristics of patients with herpes keratitis (HK) and limbal stem cell deficiency (LSCD) and identify possible factors associated with development of LSCD after HK. METHODS: In this retrospective case-series study, records of patients with a clinical diagnosis of HK seen at Massachusetts Eye and Ear over a 5-year period were reviewed for evidence of LSCD. Patient demographics, medical history, treatment, and best-corrected visual acuities (BCVAs) were recorded. RESULTS: We identified 626 patients with HK. Fifty-seven had been diagnosed with LSCD (9.3%). Thirteen percent of patients with herpes zoster keratitis (N= 25) and 7% of patients with herpes simplex keratitis (N= 32) had LSCD (P = 0.01). Keratitis caused by herpes zoster virus [odds ratios (OR), 1.77; 95% confidence interval (CI), 0.97-3.19; P = 0.01], stromal involvement (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02), and the use of topical antihypertensives (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02) were found to be associated with a higher likelihood of developing LSCD. The final logarithm of the minimum angle of resolution (LogMAR) BCVA was significantly lower in patients with LSCD compared with those without LSCD with a mean BCVA of 1.34 ± 1.52 LogMar (∼20/200) as compared to 0.18 ± 0.54 LogMar (∼20/30 ± 20/60) in those patients without LSCD (P = 0.005). CONCLUSIONS: Our data suggest that HK may be a risk factor for development of LSCD. Patients with HK should be monitored for the development of LSCD to reduce the risk of chronic ocular surface morbidity.
Cox SM, Kheirkhah A, Aggarwal S, Abedi F, Cavalcanti BM, Cruzat A, Hamrah P.
Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study. Ocul Surf 2021;22:135-142.
AbstractPURPOSE: To evaluate corneal subbasal nerve alterations in evaporative and aqueous-deficient dry eye disease (DED) as compared to controls. METHODS: In this retrospective, cross-sectional, controlled study, eyes with a tear break-up time of less than 10 s were classified as DED. Those with an anesthetized Schirmer's strip of less than 5 mm were classified as aqueous-deficient DED. Three representative in vivo confocal microscopy images were graded for each subject for total, main, and branch nerve density and numbers. RESULTS: Compared to 42 healthy subjects (42 eyes), the 70 patients with DED (139 eyes) showed lower total (18,579.0 ± 687.7 μm/mm2 vs. 21,014.7 ± 706.5, p = 0.026) and main (7,718.9 ± 273.9 vs. 9,561.4 ± 369.8, p < 0.001) nerve density, as well as lower total (15.5 ± 0.7/frame vs. 20.5 ± 1.3, p = 0.001), main (3.0 ± 0.1 vs. 3.8 ± 0.2, p = 0.001) and branch (12.5 ± 0.7 vs. 16.5 ± 1.2, p = 0.004) nerve numbers. Compared to the evaporative DED group, the aqueous-deficient DED group showed reduced total nerve density (19,969.9 ± 830.7 vs. 15,942.2 ± 1,135.7, p = 0.006), branch nerve density (11,964.9 ± 749.8 vs. 8,765.9 ± 798.5, p = 0.006), total nerves number (16.9 ± 0.8/frame vs. 13.0 ± 1.2, p = 0.002), and branch nerve number (13.8 ± 0.8 vs. 10.2 ± 1.1, p = 0.002). CONCLUSIONS: Patients with DED demonstrate compromised corneal subbasal nerves, which is more pronounced in aqueous-deficient DED. This suggests a role for neurosensory abnormalities in the pathophysiology of DED.
Coyle S, Khan MN, Chemaly M, Callaghan B, Doyle C, Willoughby CE, Atkinson SD, Gregory-Ksander M, McGilligan V.
Targeting the NLRP3 Inflammasome in Glaucoma. Biomolecules 2021;11(8)
AbstractGlaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30-40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.