Prominent Corneal Nerves Research Articles

Familial medullary thyroid cancer and prominent corneal nerves: clinical and genetic analysis

Familial medullary thyroid cancer and prominent corneal nerves: clinical and genetic analysis

Ocular manifestations of Hansen's disease.

A detailed ophthalmic evaluation including slitlamp biomicroscopy, measurement of corneal sensitivity using Cochet and Bonnet aesthesiometer, Schirmer's test and Goldmann applanation tonometry was carried out in 89 patients of Hansen's disease attending the leprosy clinic with or without ocular symptoms and willing to undergo eye evaluation. Thirty-one patients had lepromatous leprosy (8 with erythema nodosum leprosum), 56 patients had borderline disease (13 with reversal reactions) and 2 had tuberculoid disease. In addition to the well documented changes of lagophthalmos (6.7%), uveitis (7.3%) and cataracts (19%), we noted prominent corneal nerves in 133 eyes (74.7%), beaded corneal nerves in 19 eyes (10.7%), corneal scarring in 10 eyes (5.6%), corneal hypoaesthesia in 51 eyes (28%) and dry eye in 18 eyes (13%). Beaded corneal nerves and/or stomal infiltrates occurred mainly in the lepromatous group (75%). Ocular hypotony (IOP less than 12 mm Hg) was not seen more frequently in Hansen's as compared to age and sex matched controls with refractive errors or cataracts (33.7%, vs. 37.8%, p = 0.33). Our study highlights the primary corneal involvement with corneal neuropathy as the predominant feature of Hansen's disease.

Prominent corneal nerves in patients with multiple endocrine neoplasia type 2A: diagnostic implications.

We examined corneal nerves of 22 patients from 10 families with multiple endocrine neoplasia type 2A (MEN-2A). According to the findings in slit-lamp biomicroscopic examination and photographic documentation, the increased visibility of corneal nerves were classified into 5 grades (Grade 0 = invisible to Grade 4 = as thick as in MEN-2B). All eyes of normal subjects, 19 of 20 eyes of patients with anterior keratoconus, and 11 of 12 eyes of patients with non-hereditary medullary thyroid carcinoma (MTC) were either grade 0 or 1, and the remaining 2 eyes were evaluated as grade 2. Of the 44 eyes of MEN-2A patients, 5 (11.4%) eyes were grade 0, 11 (25%) eyes were grade 1, 19 (43.2%) eyes were grade 2, 8 (18.2%) eyes were grade 3, and 1 (2.3%) eye was grade 4. Thus, more than 60% of eyes of MEN-2A patients showed pathologically thickened corneal nerves of varying degree (grade 2 or higher). There was no definite relationship between the grade of corneal nerve thickening and the patient's age or presence of pheochromocytoma. Differences in the grade of corneal nerve thickening were observed among affected members belonging to the same MEN-2A family, but unaffected members of the family never showed prominent corneal nerves of grade 2 or higher. Our findings suggest that MTC patients with thickened corneal nerves might actually be MEN-2A patients and should be carefully followed for other components of this syndrome.

Ocular manifestations of Noonan syndrome.

Noonan syndrome is a genetic condition inherited in an autosomally dominant manner, characterised by congenital heart disease, short stature, abnormal facies and the somatic features of Turner's syndrome, but a normal Karyotype. The ophthalmological and orthoptic findings on 58 patients with Noonan syndrome are reported. External features were hypertelorism (74%), downward sloping palpebral apertures (38%), epicanthic folds (39%) and ptosis (48%). The orthoptic examination revealed strabismus in 48%, refractive errors in 61%, amblyopia in 33%, and nystagmus in 9% of cases. Sixty-three per cent of cases had anterior segment changes consisting of: Prominent corneal nerves (46%), anterior stromal dystrophy (4%), cataracts (8%) and panuveitis (2%). Fundal changes occurred in 20% of the study group, including optic nerve head drusen, optic disc hypoplasia, colobomas and myelinated nerves. Forty-seven per cent required non surgical treatment and a further 16% had undergone surgery for strabismus or ptosis. Only three patients had no visual defects. With such a high incidence of ophthalmic abnormalities it is clearly important that children with Noonan syndrome are screened by an ophthalmologist at an early age.

Multiple Endocrine Neoplasia Type III

The multiple endocrine neoplasia (MEN) syndromes are autosomally dominant inherited disorders in which hyperplastic or neoplastic changes occur in a wide variety of tissues. The specific syndromes are classified according to the endocrine glands affected. MEN type I consists of an aggregation of tumors of parathyroid, pancreatic, and pituitary glands. The association of medullary carcinoma of the thyroid (MCT) and pheochromocytoma is called MEN type II or type IIA, and if combined with mucosal neuromas, intestinal ganglioneuromatosis, and prominent corneal nerves, is named MEN type III or type IIB. Individuals afflicted with MEN type III are characterized by a marfanoid habitus, mucosal neuromas involving oral and ocular tissues, and a number of ophthalmologic findings including prominent corneal nerves, thickened eyelids, and subconjunctival neuromas. These features are easily recognized during the ocular exam, allowing the ophthalmologist to make an early diagnosis of this syndrome prior to the onset of life-threatening manifestations like medullary thyroid carcinoma and pheochromocytoma.

Incidence of Prominent Corneal Nerves in Multiple Endocrine Neoplasia Type 2A

We studied the increased visibility of corneal nerves inside an 8-mm diameter central corneal area in 14 patients with multiple endocrine neoplasia type 2A, one patient with multiple endocrine neoplasia type 2B, five patients with nonhereditary medullary thyroid carcinoma, ten patients with anterior keratoconus, and ten normal subjects. We used a grading system (grade 0 through grade 4) for nerve visibility based on slit-lamp biomicroscopic examination and photographic documentation. All 20 normal eyes showed either grade 0 or grade 1, which indicated no pathologic thickening of corneal nerves. Sixteen of the 28 eyes (57%) with multiple endocrine neoplasia type 2A, however, were evaluated as grade 2 or higher, which indicated thickened corneal nerves. The incidence of high nerve visibility in eyes with multiple endocrine neoplasia type 2A was significantly greater compared to normal eyes (P less than .0001), anterior keratoconus (P less than .0001), and nonhereditary medullary thyroid carcinoma (P = .0012). Furthermore, eight of the 28 eyes (29%) with multiple endocrine neoplasia type 2A showed markedly prominent corneal nerves (grade 3 and 4), a prominence similar to those seen in eyes with multiple endocrine neoplasia type 2B. There was no definite relationship among prominent nerve, age of the patient, and occurrence of pheochromocytoma. These findings suggest that over half of all patients with multiple endocrine neoplasia type 2A show corneal nerves pathologically thickened to different degrees.

Ocular changes in reactions in leprosy.

A study of ocular changes in reactions in leprosy was undertaken to assign these changes, their proper place in the wide spectrum of ocular morbidity in leprosy. 76.1% of eyes of Type I reaction and 89.7% of eyes with Type II reaction showed some ocular involvement. Corneal hypoaesthesia, superficial punctate keratitis, a decrease of corneal film break up time (BUT), prominent corneal nerves, pigment on the endothelium of the cornea and a pigmented trabecular meshwork were the common ocular findings. The incidence of iridocyclitis in Type II reactions was low (8.1%). The significance of the ocular involvement in reactions in leprosy and the pathogenesis of iridocyclitis in Type II reactions is discussed.

876 MULTIPLE ENDOCRINE NEOPLASIA (MEN) TYPE III AND UROLOGIC ABNORMALITIES

The association of thyroid medullary carcinoma, pheochromocytoma, mucosal neuromas and characteristic physical features has been designated MEN III. A case is documented with previously unreported urologic abnormalities and incidental G6PD deficiency. An 11 year old girl presented with growth retardation, chronic diarrhea, enuresis, recurrent urinary tract infections, neurogenic bladder, hydroureters and hydronephrosis. She had a Marfan-like appearance, thickened eyelids and lips, tongue nodules,prominent corneal nerves, joint laxity and muscle wasting. Cervical adenopathy was present, but no palpable thyroid nodules, abdominal organomegaly or masses. Studies showed a “cold” nodule on thyroid scan, a suprarenal mass by ultrasound, multiple lytic lesions on skeletal survey and an extradural mass on myelogram. There was a markedly increased urinary VMA and plasma epinephrine, norepinephrine, CEA (380 ng/ml, normal<2.5) and calcitonin (154,500 pg/ml, normal 30-135). Biopsy of rib lesion showed infiltration by small round tumor cells filled with numerous membrane delimited secretory granules, consistent with a neural crest origin. Since the neurogenic bladder may reflect a disorder of autonomic innervation, its association with tumors of neuroectodermal origin suggests a common underlying defect of embryonal migratory neuroblastic elements.

Histologic Study of the Ocular Lesions in Multiple Endocrine Neoplasia Syndrome Type IIb

We studied the clinical and histopathologic findings in the eyes of two patients with multiple endocrine neoplasia type IIb. A prominent clinical feature of this condition is enlarged nonmyelinated corneal nerves composed of bundles of axons associated with Schwann cells. Prominent corneal nerves within an otherwise normal corneal stroma are an important clinical feature of multiple endocrine neoplasia type IIb. Because of this, ophthalmologists are in a position to make an early diagnosis and hence to recommend diagnostic procedures and treatment for the associated potentially fatal medullary carcinoma of the thyroid and pheochromocytomas.