The combination of diabetes mellitus and hypertension is the leading cause of end-stage renal disease (ESRD) in the United States (1). Because of better health care, more and more of these patients are living longer, and many are candidates for renal transplantation (2). Before transplantation, during the evaluation process, the visual acuity of potential recipients should be determined. Patients with any type of diabetes should have a full ophthalmologic evaluation. Although poor vision or blindness is not a reason to deny transplantation, special arrangements for medication dispensing and transport to follow-up visits must be established prior to transplantation (3).

After transplantation, during all follow-up encounters, the practitioner should routinely ask each patient about any visual changes, in addition to determining when their last ophthalmologic visit was. Annual follow-up is indicated for any patient with prior ocular pathology, and more frequent follow-up is indicated for subjects with diabetes (4). In addition, the risk for visual disturbances is increased during the first 3 months after a pancreas transplant alone (PTA) or a pancreas after kidney (PAK) transplantation due to the frequent use of warfarin in an effort to prevent thrombosis of the allograft. Early during the postoperative phase, careful attention should be directed at the risk of retinal neovascularization. During the Diabetes Control and Complications Trial, an increase in diabetic retinopathy was observed after rapid normalization of blood sugars in the intensive insulin regimen group (5). Given this result, there is concern that the euglycemic state established after pancreas transplantation might also lead to an increased risk of neovascularization. Therefore, close ophthalmologic follow-up is
necessary after simultaneous pancreas kidney (SPK), PAK or PTA transplantation. Studies to establish the regression of diabetic retinopathy after pancreas transplantation, with or without kidney transplantation, have yielded variable results. To date, there is no incontrovertible evidence that pancreas transplantation leads to a better visual outcome as compared with intensive glycemic control alone (6). The regression of hypertensive retinopathy, by contrast, has been well-documented following renal transplantation and normalization of systemic blood pressure (7).

Corneal or conjunctival calcification is a common complication for subjects with ESRD on hemodialysis (8). Tissue injury from abnormal calcium and phosphorus metabolism, in the setting of decreased lubrication and tear formation associated with dialysis, likely contributes to the development of these ocular changes. However, corneal calcifications were not found to be more common after renal transplantation (1).

As transplant recipients survive longer (9), the need to control nondiabetic vasculopathy takes greater importance. Chronic kidney disease (CKD) and dialysis are associated with high cardiovascular morbidity. In transplant patients, a vasculopathy develops which represents a progression of preexisting arteriosclerosis that developed during the course of the patient’s renal failure and time on dialysis (10). After transplant, hyperlipidemia, medications and hypertension may lead to further progression of these vascular changes. This vasculopathy affects the delicate and essential vasculature of the retinal, choroid and optic nerve, which have been shown to deteriorate after transplantation (10).

Given the risk for this vasculopathy, all transplant patients should be screened and treated for lipid abnormalities. Smoking should be strongly discouraged, and all patients should be considered for treatment with aspirin or other antiplatelet adhesion agents (11).

Immunosuppression is required for allograft survival. It was the introduction of 6-mercaptopurine and azathioprine during the 1950s that set the stage for successful allograft transplantation (12). In the 1960s, glucocorticoids were added for induction (13) and maintenance immunosuppression, and high-dose steroids were introduced for the treatment of acute rejection. Unfortunately, ocular side effects are not uncommon. Lens opacification, specifically posterior subcapsular cataract formation (Fig. 35.1), is associated with glucocorticoid use (14). The absence of cataracts before transplantation, the rapid development of them after transplant, and the high incidence of them amongst transplant patients when compared to age-matched controls (45% vs. 10%) (14) are consistent for a role of steroids in cataract formation. The incidence of posterior subcapsular cataracts in patients treated with a prolonged course of steroids has ranged from 10% to 50% with up to 20% of patients developing symptomatic visual impairment (1, 2, 3). Studies have demonstrated a dose-dependent relationship between corticosteroid therapy and cataract formation. Both the total dose of steroids given to a patient (15) and the frequency and amount of high dose pulse steroid exposure has been recognized to be a risk factor for cataract formation (16). Individual susceptibility and genetic factors likely also play a role (15). Cataracts develop more often and become symptomatic earlier posttransplant in elderly and diabetic patients (15).

In most transplant recipients, the prognosis for good vision after cataract extraction and lens implantation is excellent (17). Diabetics who have macular edema are an exception to this rule; these subjects are at higher risk for a poor visual outcome (2,4,5). Therefore, cataract extraction in these subjects should be performed before lens opacification precludes recognition and treatment of macular edema. As stated above, frequent ophthalmologic follow-up is essential in these transplant subjects with diabetes (4).

The pathological changes responsible for lens opacification and cataract formation are poorly understood. Universal theories proposed for cataract formation include: failure of osmotic regulation and localized water accumulation, free radical damage, oxidative changes in lens proteins leading to denaturation, and abnormal aggregation of lens proteins (12).

Little is known about how specific transplant medications might augment these mechanisms. Glucocorticoids and calcineurin inhibitors may alter the amount and type of growth factors reaching the aqueous humor. A role for fibroblast growth factor (FGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-β) have all been proposed (12).

Hampering progress in prevention and treatment of cataracts is the lack of understanding of the underlying mechanism by which they form. Therefore, a variety of different medications and surgical interventions have been tried. Vitamin E administration, in both an animal model and in an in vitro model of steroid-induced cataract formation, has resulted in a decreased incidence and severity of lens opacification (18). It was hypothesized that vitamin E acts as a free radical scavenger, thereby protecting lens proteins from oxidative damage. Despite many claims, no effective
treatment, other than surgical removal of the lens, is currently available for treating cataracts (12).

Increased intraocular pressure (IOP) is a serious side effect of steroid use, and is reported to occur in 5% to 10% of allograft recipients (3, 4, 5, 6, 7). The route of steroid administration appears to be a factor affecting the incidence of increased IOP, as topical steroids are associated with a higher incidence when compared to systemic steroid therapy. The mechanism by which topical steroids lead to an increase in IOP is by decreasing trabecular aqueous humour outflow. Although systemic steroids also decrease this outflow, they have the additional effect of decreasing the formation of the aqueous humor, resulting in a lower incidence of increased IOP (3). Increases in IOP are asymptomatic and can only be detected during ophthalmologic exam using a tonometer. If left untreated, these increases can lead to visual field defects, atrophy of the optic nerve, and blindness. In transplant patients, increased IOP can be treated with topical and systemic medicines, laser therapy, and surgery interventions. However, topical drops that result in miosis may decrease the visual acuity in patients who also have cataracts.

Opportunistic infection of the eye occurs at a frequency of approximately 2% in immunosuppressed patients (17).