Cataract Surgery in Diabetic Patients

Phacomulsification is nowadays the preferred technique in most types of cataract. This technique was developed by Kelman in 1967 and was not widely accepted until 1996 [45]. It results in less postoperative inflammation and astigmatism, more rapid visual rehabilitation and, with modern foldable lenses, a lower incidence of capsulotomy than with the outdated extracapsular surgery. There has been a recent shift in emphasis towards earlier cataract extraction in diabetics. Cataract surgery is advisable before lens opacity precludes detailed fundus examination. While the overall outcomes of cataract surgery are excellent, patients with diabetes may have poorer vision outcomes than those without diabetes. Surgery may cause a rapid acceleration of retinopathy, induce rubeosis or lead to macular changes, such as macular edema or cystoid macular edema [46, 47]. The worst outcomes may occur in operated eyes with active proliferative retinopathy and/or preexisting macular edema [48, 49]. In diabetics with or without evidence of diabetic retinopathy the blood-aqueous barrier is impaired leading to an increased risk of postoperative inflammation and development of a sight-threatening macular edema, a process that is exacerbated by cataract surgery [5052]. Factors that influence the amount of postoperative inflammation and the incidence of clinical and angiographic cystoid macular edema are duration of surgery, wound size and posterior capsular rupture or vitreous loss. Liu et al. showed that phacoemulsification surgery affects the blood-aqueous barrier more severely in diabetic patients with proliferative diabetic retinopathy than in patients with nonproliferative diabetic retinopathy or nondiabetic patients [53]. An analysis of Medicare beneficiaries ( ) from the years 1997 through 2001 revealed that the rate of cystoid macular edema diagnosis after cataract surgery was statistically significantly higher in diabetic patients than in nondiabetics [54]. Several clinical studies investigated the role of phacoemulsification cataract surgery on the progression of diabetic retinopathy. One year after cataract surgery, the progression rate of diabetic retinopathy ranges between 21% and 32% [5558]. Borrillo et al. reported a progression rate of 25% after a follow-up period of 6 months [59]. A retrospective review of 150 eyes of 119 diabetic patients undergoing phacoemulsification surgery showed a similar progression of diabetic retinopathy in 25% of cases within the follow-up period of 610 months [56]. A prospective study evaluating the onset or worsening of macula edema at 6 months following cataract surgery in patients with mild or moderate nonproliferative diabetic retinopathy reported an incidence of 29% (30 of 104 eyes) of macula edema based on angiographic data [60]. Krepler et al. investigated 42 patients undergoing cataract surgery and reported a progression of diabetic retinopathy of 12% in operated versus 10.8% in nonoperated eyes during the follow-up of 12 months [61]. During the same follow-up period of 12 months, Squirrell et al. showed that out of 50 patients with type 2 diabetes undergoing unilateral phacoemulsification surgery 20% of the operated eye and 16% of the nonoperated had a progression of diabetic retinopathy [62]. Liao and Ku found in a retrospective study that out of 19 eyes with preoperative mild to moderate nonproliferative diabetic retinopathy 11 eyes (57.9%) showed progression of diabetic retinopathy 1 year after surgery, while 12 eyes (63.2%) had progressed 3 years postoperatively. The progression rates were statistically significant when compared to eyes without preoperative retinopathy [63]. A recently published prospective study evaluated eyes from 50 diabetic patients with and without retinopathy after cataract surgery by optical coherence tomography [64]. The authors reported an incidence of 22% for macula edema following cataract surgery (11 of 50 eyes) while macula edema did not occur in eyes without retinopathy. When only eyes with confirmed diabetic retinopathy were evaluated ( ), the incidence for postoperative macula edema and cystoid abnormalities increased to 42% (11 of 26 eyes). Minimal changes from baseline values in center point thickness were observed in eyes with no retinopathy. Eyes with moderate nonproliferative diabetic retinopathy or proliferative diabetic retinopathy developed an increase from baseline of 145 m and 131 m at 1 month and 3 month, respectively. The difference in retinal thickening between the 2 groups at 1 and 3 months was statistically significant and among patients with retinopathy inversely correlated with visual acuity improvements.

5. Anticataract Treatment
5.1. Aldose-Reductase Inhibitors Aldose reductase inhibitors (ARI) comprise a variety of structurally different compounds like plant extracts, animal tissues or specific small molecules. In diabetic rats, plant flavonids, such as quercitrin or the isoflavone genistein, have delayed diabetic cataract formation [6568]. Examples of natural products with known AR inhibitory activity are extracts from indigenous plants like Ocimum sanctum, Withania somnifera, Curcuma longa, and Azadirachta indica or the Indian herbal Diabecon [69, 70]. Levels of polyol in the lenses of rats have been reduced by injection of intrinsic ARI containing extracts from human kidney and bovine lenses [71]. Nonsteroidal anti-inflammatory drugs, such as sulindac [72, 73], aspirin [74, 75] or naproxen [76] have been reported to delay cataract in diabetic rats through a weak AR inhibitory activity. Several experimental studies support the role of ARI in preventing and not only delaying diabetic cataract formation. In a rat model of diabetes, animals were treated with the AR inhibitor Renirestat [77]. The study reported a reduction of sorbitol accumulation in the lens as compared to untreated diabetic rats. Furthermore, in Ranirestat treated diabetic rats there were no signs of lens damage like degeneration, swelling, or disruption of lens fibers throughout the treatment period in contrast to the untreated group. In a similar study, diabetic rats were treated with a different ARI, Fidarestat [78]. Fidarestat treatment completely prevented cataractous changes in diabetic animals. In dogs the topically applied ARI Kinostat has been shown to reverse the development of sugar cataracts [79].

Other ARI with a beneficial effect on diabetic cataract prevention encompass Alrestatin [80], Imrestat [81], Ponalrestat [82], Epalrestat [83], Zenarestat [84], Minalrestat [85], or Lidorestat [86]. These studies provide a rationale for a potential future use of ARI in the prevention or treatment of diabetic cataracts. 5.2. Antioxidant Treatments of Diabetic Cataracts As oxidative damage occurs indirectly as a result of polyol accumulation during diabetic cataract formation, the use of antioxidant agents may be beneficial. A number of different antioxidants have been reported to delay cataract formation in diabetic animals. These include the antioxidant alpha lipoic acid, which has been shown to be effective in both delay and progression of cataract in diabetic rats [87]. Yoshida et al. demonstrated that the combined treatment of diabetic rats with vitamin E, a lipid-soluble and antioxidant vitamin, and insulin synergistically prevented the development and progression of cataracts in the animals [88]. Pyruvate, an endogenous antioxidant, has recently gained attention for its inhibitory effect on diabetic cataract formation by reducing sorbitol formation and lipid peroxidation in the lens [89]. A study performed by Varma et al. showed that the incidence of cataract in diabetic rats was lower in the pyruvate-treated group than in the untreated control group [ 90]. Additionally, the severity of opacities in the pyruvate-treated rats was minor than in the control animals. The beneficial effect of pyruvate in the prevention of cataract is mainly attributed to its effective scavenging ability for reactive oxygen species generated by increased levels of sugars in diabetic animals [91]. However, clinical observations in humans suggest that the effect of antioxidant vitamins on cataract development is small and may not prove to be clinically relevant [92]. 5.3. Pharmacological Agents for the Treatment of Macular Edema Following Cataract Surgery Proinflammatory prostaglandins have been shown to be involved in the mechanisms leading to fluid leakage from perifoveal capillaries into the extracellular space of the macular region [93]. Due to the ability of topical nonsteroidal anti-inflammatory drugs (NSAIDs) to block the cyclooxygenase enzymes responsible for prostaglandin production, studies suggested that NSAIDs may also reduce the incidence, duration and severity of cystoid macular edema [9497] by inhibiting the release and breakdown of the blood-retina barrier [98, 99]. Nepafenac, a topical NSAID indicated for the prevention and treatment of anterior segment pain and inflammation after cataract surgery, has been used recently in clinical trials to test its efficacy in reducing the incidence of macular edema after cataract surgery. The active ingredient is a prodrug that rapidly penetrates the cornea to form the active metabolite, amfenac, by intraocular hydrolases particularly in the retina, ciliary body epithelium and choroid [100]. A retrospective study compared the incidence of macular edema after uneventful phacoemulsification between 240 patients treated for 4 weeks with topical prednisolone and 210 patients treated with a combination of prednisolone and nepafenac for the same time. The authors concluded that patients treated with topical prednisolone alone had a statistically significantly higher incidence of macular edema than those treated with additional nepafenac [101].

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