Systemic Disorders With Corneal Changes

PATHOGENESIS At present, at least 8 MPS syndromes have been described, all of which are autosomal recessive, with the exception of Hunter syndrome, which is X-linked. Specific enzyme defects and genetic mutations have been identified for each of the syndromes. There is variation in phenotypic expression. For example, the three “MPS I” disorders (Hurler, Scheie, and Hurler-Scheie) result from different amino acid substitutions that result in a defect in α-L-iduronidase. Hurler syndrome (MPS I-H) is the most severe of the the three, with systemic signs of severe cognitive impairment and with corneal clouding appearing by 1 year of age. The life span of patients with Hurler syndrome is very limited unless a bone marrow transplant is performed. In contrast, symptoms of Scheie syndrome (MPS I-S) do not appear until the ages of 5–15. Although corneal clouding occurs, children with this syndrome generally have normal intelligence and a normal life span. Hurler-Scheie syndrome (MPS I-HS) is an intermediate form and is thought to result from the transmission of 1 Hurler gene and 1 Scheie gene.

CLINICAL FINDINGS Characteristic clinical findings are listed in Table 11-1. Ophthalmic manifestations of most MPS syndromes include corneal clouding, retinopathy, and optic atrophy. Clouding generally involves the entire cornea and may or may not be present at birth. It is often slowly progressive from the periphery toward the center and can cause serious reduction in vision.

LABORATORY EVALUATION Urine can be screened for the presence of GAGs, but the most precise method of diagnosing the various MPS disorders is through a leukocyte or plasma enzyme assay. Confirmation of the disease can also be demonstrated using a conjunctival biopsy, although this is rarely necessary.

MANAGEMENT Penetrating keratoplasty (PK) may be considered in the management of corneal clouding in MPS, although the patient’s mental status or retinal or optic nerve abnormalities may limit visual improvement. Deep anterior lamellar keratoplasty has recently been used in patients with MPS (Fig 11-1). However, the prognosis for keratoplasty in MPS is considered guarded, as the abnormal storage material may accumulate again in the graft. Some regression of corneal clouding following successful donor stem cell bone marrow transplantation occurs in about one-third of patients. Enzyme replacement therapy is being used for several of the MPS syndromes, and gene transfer therapy is under investigation.

Figure 11-1 A, Hurler syndrome manifesting visually significant corneal clouding. B, Clear corneal graft after deep anterior

lamellar keratoplasty. (Courtesy of Roberto Pineda II, MD.)

Diabetes Mellitus

The most common disorder of carbohydrate metabolism, diabetes mellitus (DM), has nonspecific corneal manifestations of punctate epithelial erosions, basement membrane changes resembling epithelial basement membrane dystrophy, Descemet folds, and decreased corneal sensation. DM is discussed at length in BCSC Section 12, Retina and Vitreous, although the emphasis in that volume is on retinal rather than corneal aspects of the disease.

PATHOGENESIS Patients with DM have ultrastructural abnormalities of the basement membrane complex that contribute to problems of epithelial–stromal adhesion. These abnormalities include thickening of the multilaminar basement membrane, reduced hemidesmosome number, and decreased penetration of anchoring fibrils. Accumulation of polyols such as sorbitol by the action of aldose reductase on excess glucose may contribute to the alterations in the epithelium and endothelium and the corneal hypoesthesia seen in these patients. Reduced corneal nerve density and nerve branching in DM have been demonstrated by confocal microscopy and can be correlated with the degree of neuropathy.

CLINICAL FINDINGS Corneal epithelial surface changes and hypoesthesia occur with increasing severity and increasing duration of the disease. Removal of diabetic epithelium at surgery results in the loss of the basal cells and basement membrane, often leading to prolonged healing difficulties. Faint vertical folds in Descemet membrane and deep stroma (Waite-Beetham lines) are not specific to DM but may represent early endothelial dysfunction and increased stromal hydration.

LABORATORY EVALUATION Glycosylated hemoglobin is related to poor control of DM and may correlate with poor corneal healing in addition to progressive retinopathy.

MANAGEMENT DM is not a contraindication to PK or other corneal surgery. Measures that can improve diabetic epitheliopathy include the following:

perioperative management of meibomian gland dysfunction (increased comorbidity with DM) minimizing epithelial debridement at surgery

increasing lubrication avoiding toxic medications