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At least 19 recordsLinked to original sources
PubMed2025

Aging and Corneal Nerve Health: Mechanisms of Degeneration and Emerging Therapies for the Cornea.

Corneal nerves play a crucial role in maintaining ocular surface homeostasis by supporting the functional integrity of corneal epithelial, stromal, and endothelial cells; modulating tear secretion; and facilitating sensory responses essential for overall ocular health. With advancing age, these highly specialized peripheral sensory fibers undergo progressive attrition and morphologic distortion driven by the canonical hallmarks of aging including genomic instability, impaired proteostasis, mitochondrial dysfunction, and chronic low-grade inflammation. The resulting neuro-immune dysregulation reduces trophic support, delays wound healing, and predisposes older adults to dry-eye disease, neurotrophic keratopathy, and postsurgical hypoesthesia. Age-exacerbating cofactors including diabetes, dyslipidemia, neurodegenerative disorders, topical preservatives, chronic contact-lens wear, herpes zoster ophthalmicus, and ocular-surface hypoxia further accelerate sub-basal nerve rarefaction and functional decline. This review provides an overview of age-related physiological alterations in ocular surface nerves, with a particular emphasis on corneal innervation. It also discusses risk factors that speed up these changes. Given the inherently limited regenerative capacity of corneal nerves and their inability to fully restore to baseline conditions following injury or degeneration, it is critical to identify and develop effective strategies aimed at mitigating or delaying physiological nerve degeneration and promoting nerve regeneration. This review also brings up emerging therapeutic strategies, including regenerative medicine, neuroprotective agents, and lifestyle interventions aimed at mitigating age-related corneal nerve degeneration.

Humans↗
PubMed1978

Corneal nerve access in monkeys.

Electron microscopical examination of corneal nerves in rhesus and cynomolgous monkeys revealed that limbal, subepithelial nerves gained direct access to the corneal epithelium. Epithelial axons occurred singly and infrequently and they were confined to the basal layer of cells. All nerves of the stroma terminated within the layer and rami perforans were not found. The apparent barrier to nerve passage presented by Bowman's layer in monkeys was discussed in relation to primates in general. The isolation of stromal and epithelial nerve fibres confirms that terminals occur in both layers and their respective potential for excitation was briefly discussed.

Animals↗
PubMed1978

Ultrastructure of the corneal nerves after fixation with potassium permanganate.

The innervation of the rat cornea was investigated electron microscopically after KMnO4 fixation. Myelinated nerve fibres were observed only in the limbal margin of the cornea, whereas the axons located in the stroma of the avascular cornea were surrounded by the Schwann cell cytoplasm. Axon profiles with small (300-500 A) granular vesicles and another type with agranular vesicles were seen among the non-vesiculated fibres in all parts of the cornea. After superior cervical ganglionectomy it was not possible to find any axons with small granular vesicles. On the other hand, sone degenerating axon profiles were observed in the stromal nerve trunks after ganglionectomy. In the epithelium-naked axons with an occasional mitochondrion and a few agranular vesicles penetrated between the epithelial cells. Moreover, axons filled with several mitochondria were rarely observed in the epithelium, but these were difficult to differentiate from the surrounding epithelial cells. The role of the different nerve types observed in the cornea is discussed. The results suggest that the rat cornea has a dual vegetative innervation.

Animals↗
PubMed1979

Fine structure of sensory nerves in the rat cornea: an experimental nerve degeneration study.

Fine structure of nerve fibres and terminals in the rat cornea was studied after fixation with glutaraldehyde and osmium tetroxide or with potassium permanganate. Superior cervical and/or ciliary ganglionectomy as well as ophthalmic neurotomy were performed in order to verify the origin of the corneal nerves. In the control corneas axon profiles with granular vesicles were observed in the stroma. Other axons containing agranular vesicles were found both in the stroma and in the epithelium. Superior cervical ganglionectomy abolished only the axons containing granular vesicles but did not affect the corneal blink reflex. Ciliary ganglionectomy induced more conspicuous changes in both stromal and intraepithelial axon profiles. The corneal reflex was, however, normal. Some of the axons containing agranular vesicles also showed degenerative changes. However, intact axon profiles with agranular vesicles were seen even after extirpation of both the ciliary ganglion and the superior cervical ganglion (combined autonomic ganglionectomy). On the other hand, all axon profiles with agranular vesicles disappeared after coagulation of the ophthalmic and maxillary nerves (sensory denervation). This operation destroyed most of the axons in all parts of the cornea and abolished the blink reflex. It is concluded that the axon profiles in the corneal epithelium, containing agranular vesicles, are sensory axons of the trigeminal nerve. A possible role of the vesicles in sensory nerves is discussed.

Animals↗
PubMed1979

Multiple endocrine neoplasia, type 2b: phenotype recognition; neurological features and their pathological basis.

Sixteen patients affected with multiple endocrine neoplasia, type 2b (MEN 2b), were evaluated by clinical, neurological, nerve conduction and electromyographic, and postmortem examinations. Eight of the 11 patients examined clinically had symptoms: 5, neurogenic constipation; 1, failing vision due to hypertrophied corneal nerves; 1, neuromuscular symptoms and pes cavus; and 1, facial disfigurement. Expression of the dominantly inherited MEN 2b gene is more variable than previously known. When neuromuscular findings are present alone, the features may be those of peroneal muscular atrophy. Because 10 of the 11 patients had sufficiently full expression of the dominantly inherited gene--"Marfanlike" body build, full and fleshy lips, whitish yellow nodules (neuromas) on the tip and edges of the tongue, pes cavus, or peroneal muscular atrophy--the presence of MEN 2b was recognized and a search for the usually associated medullary thyroid carcinoma was instigated. In addition to the recognized involvement of autonomic nerves, we have confirmed that somatic motor and senory neurons may be involved. Findings at postmortem evaluation indicate that symptoms can be attributed to neuroma formation: a characteristic adventitious plaque of tissue composed of hyperplastic, interlacing bands of Schwann cells and myelinated fibers overlay the posterior columns of the spinal cord.

Adolescent↗
PubMed2026

Astigmatic vector outcomes after FS-LASIK versus SMILE for high myopic astigmatism: a single-center retrospective comparative cohort study without cyclotorsion compensation.

PURPOSE: To compare astigmatic correction vector outcomes between femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE, also termed Keratorefractive Lenticule Extraction, KLEx) without intraoperative cyclotorsion compensation in patients with high myopic astigmatism (-&#x2009;2.00 to&#x2009;-&#x2009;3.75 D), and to clarify procedure-specific correction tendencies under this non-standardized alignment protocol. METHODS: This single-center retrospective comparative cohort study enrolled 155 eyes (one eye randomly selected per patient) that underwent FS-LASIK (80 eyes) or SMILE/KLEx (75 eyes) for high myopic astigmatism correction from January 2023 to July 2024 in Beijing Fenglian Jiayue Lige Clinic. Intraoperative cyclotorsion compensation was intentionally disabled to isolate inherent procedural astigmatism correction characteristics. Standardized Alpins vectorial analysis was performed at 3&#xa0;months and 12&#xa0;months postoperatively. PRIMARY ENDPOINT: 12-month Alpins correction index (CI). Multivariable propensity score adjustment was applied to mitigate confounding by clinical treatment selection bias. Statistical multiplicity control was implemented for secondary vector and visual outcomes. RESULTS: Baseline demographic, refractive, corneal and ocular biometric parameters were balanced between groups after propensity matching. No statistically significant intergroup differences were detected in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual cylinder, safety index or efficacy index at 3 and 12&#xa0;months (all P&#x2009;>&#x2009;0.05). Under the non-cyclotorsion-compensated protocol, significant intergroup differences were identified in the magnitude of surgically induced astigmatism (SIA), correction index (CI), and magnitude error (ME) at both follow-up timepoints (all P&#x2009;<&#x2009;0.0001). Target induced astigmatism (TIA), difference vector (DV), index of success (IOS), and angle error (AE) magnitudes were comparable between groups (all P&#x2009;>&#x2009;0.05). The vector mean axis of DV differed significantly between groups at 3 and 12&#xa0;months (Watson-Williams circular test, all P&#x2009;<&#x2009;0.0001). No reoperations were documented in clinic medical records for either cohort. No standardized dry eye questionnaires, tear film testing or corneal nerve density metrics were collected to quantify dry eye adverse events; only unstructured clinical notes were reviewed for complication screening. CONCLUSIONS: Under surgical alignment without cyclotorsion compensation, FS-LASIK and SMILE/KLEx both yielded acceptable visual and refractive safety/efficacy for high myopic astigmatism (-&#x2009;2.00 to&#x2009;-&#x2009;3.75 D) at 1-year follow-up, but demonstrated divergent astigmatism correction tendencies: FS-LASIK exhibited relative astigmatism overcorrection (vector mean DV:&#x2009;-&#x2009;0.35&#x2009;&#xb1;&#x2009;0.43 D&#x2009;&#xd7;&#x2009;91&#xb0;, CI&#x2009;>&#x2009;1), while SMILE/KLEx showed relative undercorrection (vector mean DV:&#x2009;-&#x2009;0.21&#x2009;&#xb1;&#x2009;0.53 D&#x2009;&#xd7;&#x2009;12&#xb0;, CI&#x2009;<&#x2009;1). These correction biases are specific to the study's manual limbal alignment protocol without cyclotorsion tracking and cannot be generalized to modern optimized surgical platforms equipped with automated cyclotorsion compensation. Residual refractive errors across both groups are likely multifactorial, including differential corneal stromal healing responses, divergent femtosecond/excimer laser tissue modification mechanisms, and uncorrected intraoperative ocular cyclotorsion.

Humans↗
PubMed1977

Multiple endocrine adenomatosis type IIB. Report of two cases and review of the literature.

The combination of bilateral medullary thyroid cancer, bilateral pheochromocytoma, Marfanoid body habitus with arachnodactyly, pectus excavatum, mucosal neuromas, and hyperplastic corneal nerves has become recognized as a definite entity, multiple endocrine adenomatosis (MEA) Type IIB. Two cases of MEA Type IIB are described, along with diagnosis, treatment, pitfalls in management, and related syndromes. When this syndrome is suspected, a careful search for other hyperfunctioning endocrine glands, particularly pheochromocytoma, must be made. Failure to recognize pheochromocytoma may prove a serious hazard if thyroidectomy is the initial procedure. The value of thyrocalcitonin as an indicator of the presence of medullary thyroid cancer and its value as a familial screening test are discussed.

Adolescent↗
PubMed1978

Syndrome of multiple mucosal neurofibromas, pheochromocytoma and medullary thryoid carcinoma. Report of a case.

The present article reports a case of multiple endocrine neoplasia (MEN) syndrome, type IIb, including the following components: pheochromocytoma, medullary thyroid carcinoma, hyperplastic corneal nerves and multiple mucosal oral and ocular neurofibromas. The patients, a 35-year-old male also exhibited a series of other pertinent findings, i.e. thickened eyelids, marfanoid habitus and widened mandibular canal and mental foramina. In the discussion the clinical and histopathologic characteristics of the present case are compared with similar findings in other previously published cases. The multiple oral mucosal neurofibromas are described clinically and histopathologically and are stated as a pathognomonic early sign of the syndrome.

Adult↗
PubMed1975

Multiple endocrine adenomatosis type IIb. Diagnosis and treatment.

A 29-year-old man with a marfanoid habitus, peculiar mucosal neuromas of the lips and tongue, high arched palate, hyperplastic corneal nerves, and hypertension was found at operation to have medullary carcinoma of the thyroid, parathyroid hyperplasia, and pheochromocytoma. These symptoms and findings are characteristic of multiple endocrine adenomatosis (MEA IIb) syndromes.

Adrenalectomy↗
PubMed1977

Corneal reflex latency in trigeminal nerve lesions.

Using a new technique to record the latency of the corneal reflex, we established normal values in 32 normal subjects between 10 and 80 years of age, divided into three age groups. In 15 patients with unilateral trigeminal nerve lesions, comparison of the responses on both sides permitted differentiation of afferent and efferent lesions.

Adolescent↗
PubMed1975

Localization of acetylcholinesterase in the rabbit cornea by light and electron microscopy.

Acetylcholinesterase (AChE) has been localized in the rabbit cornea by light and electron microscopy histochemical techniques. In the stroma, the enzyme is concentrated in nerves. In the epithelium, the enzyme is concentrated in intercellular spaces devoid of nerves. The morphologic appearance of the enzyme staining by light and electron microscopy in the epithelium is similar; consequently, the staining demonstrated with light microscopy examination does not always represent epithelial nerves. A significant portion of corneal acetylcholinesterase therefore appears unrelated to nerves. Considerably smaller deposits of enzyme reaction product were present in cells in every layer of the cornea, using electron microscopy histochemistry; they were not identified by light microscopy.

Acetylcholinesterase↗
PubMedDate not supplied

[Diagnosis of neurinomas of the Gasserian ganglion].

The article analyses the findings of clinical and X-ray examination in 39 patients in two types of growth of neurinoma of the gasserian ganglion: with localization within the boundaries of the middle cranial fossa (22) and with the formation of tumor nodes in the middle and posterior cranial fossae (17). The first symptoms of the disease were paresthesia or numbness and continuous pain mostly in the zone innervated by the 1st--2nd pair of the trigeminal nerve, absence of corneal reflexes, high lumbar cerebrospinal fluid pressure, and protein-cellular dissociation in the cerebrospinal fluid. The craniograms revealed destruction of the floor of the middle cranial fossa with involvement of the walls of the f. ovale, spinosum et lacerum and the apex of the pyramid of the temporal bone. Carotid angiography demonstrated typical displacement of the carotid siphon to the midline, to the front, or to the back. The middle cerebral artery was moderately displaced upward and an arched art. chorioidea, anterior was noted. Growth of the neurinoma into the posterior cranial fossa was attended with displacement and deformity of a. basilaris et cerebellaris superior and the veins of the posterior cranial fossa. The ventriculograms showed compression of the inferior horn of the lateral ventricle and moderate compression of the caudal parts of the fourth ventricle and aqueduct of Sylvius. Comprehensive generalization of all the findings gained from examination of the patient is necessary in determining the topics and type of the growth of a neurinoma of the gasserian ganglion.

Adolescent↗
PubMed1979

Birth order and parental age in microphthalmos and other ocular diseases.

We compared the distribution of birth order and maternal and paternal ages of blind school children throughout Japan with that of the total Japanese population of the corresponding age groups and with that of a subgroup of children with acquired blindness. The number of first-born children with microphthalmos was smaller, and the number of second-, third-, or fourth-born children was larger, as compared with the control groups. The differences were highly statistically significant by chi-square test. There was a less pronounced indication of birth order effect in amblyopia, congenital cataract, and optic nerve atrophy, which involved more first-borns than in the controls. The distribution of maternal age was also different from the control group in microphthalmos, congenital cataract, corneal opacity, and optic nerve atrophy. Less mothers in their 20s and more in their 30s produced children with these conditions. We believe this finding may be partly related to the rapid decline in infant mortality and in the incidence of congenital blindness in Japan.

Adult↗
PubMed1979

Corneal pain evoked by thermal stimulation.

The thermal sensitivity of the eyelid and cornea was compared using an automated apparatus to produce stimulus pulses of known magnitude and duration over the range 33--45 degrees C. Subjects reported only temperature sensation when the skin of the upper eyelid was tested; however, corneal stimulation in the same subjects was always perceived as nociceptive. The possibility that other ocular tissues may be involved in the pain responses was shown to be unlikely by direct experimentation or by calculation of heat flow in those tissues. Cornea and eyelid thresholds were compared in relationship to the structural and physical properties of these tissues. It was found that the nerve endings of the corneal epithelium are less sensitive to temperature change when compared to the thermal receptors of the eyelid. It is concluded that the cornea is useful for the experimental study of pain.

Adult↗
PubMed1979

Familial corneal hypesthesia.

A 4-year-old boy with severe, diffuse, asymptomatic, punctate, epithelial corneal erosions had bilateral sharply decreased corneal sensation with normal skin sensation in the distribution of the trigeminal nerves. Subsequent family studies disclosed five family members with similar corneal changes and decreased corneal sensation and no punctate erosions. None had decreased skin sensation in the distribution of the fifth cranial nerve. No environmental factors or evidence of local or systemic disease accounted for these findings.

Adolescent↗
PubMedDate not supplied

The ocular manifestations of herpes zoster, varicella, infectious mononucleosis, and cytomegalovirus disease.

Herpes zoster, caused by varicella-zoster (V-Z) virus which also causes varicella (chickenpox), is usually a benign self-limited disease. However, when the ophthalmic division of the trigeminal nerve is affected, the ocular disease (ophthalmic zoster), although also usually mild and self-limited, may have severe complications (corneal scarring, glaucoma, iris atrophy, posterior synechiae, scleritis, motor disturbances, optic neuritis, retinitis, anterior segment necrosis, and phthisis bulbi and servere postherpetic neuralgia). Varicella affects the eye rarely (except for the typical lid lesions), but associated conjunctival and corneal lesions, iridocyclitis, glaucoma, chorioretinitis, and optic nerve lesions have been described. Infectious mononucleosis may involve the eye either by direct involvement or from a remote focus such as the central nervous system. Ocular manifestations of cytomegalovirus disease is usually limited to the choroid and retina unless involvement of the developing embryo occurs prior to the development of the eye.

Adolescent↗