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Risk of Cataract Surgery in HIV-Infected Individuals:
A Danish Nationwide Population-Based Cohort Study
 
 
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It seems premature to presume older PLWH are not at increased risk for serious eye disease I have great concerns that aging PLWH have increased risk for cataracts, retinal detachment, and compromised outcomes. This could be due to vascular disorders in HIV, multiple comorbidities, bad circulation, previous CMD retinitis history & low nadir CD4. These authors conclude accelerated aging cannot be excluded as a risk factor. Importantly L-SOCA the NOH HIV & eye database was discontinued before it was realized aging is ap problem & this leaves us unable to gather & study data on these concerns.
 
Jules
 
www.natap.org
 
from Jules: since L-SOCA, the NIH HIV database for HIV & eye disease was discontinued we ae now unable to follow eye disease n the HIV Aging population. Several questions are ignored & need investigation, they are being ignored. Is there an increased risk for cataract surgery & for earlier surgery? Is the outcome more risky for older HIV+? Is there a greater risk for retinal detachment? And for older aging HIV+ with low nadir CD4 <200 who had CMV retinits in early days are they at greater risk for retinal detachment? Are people who never had CMV retinitis but had low CD4 nadir at increased risk for cataract surgery & for premature surgery & for increased risk for future retinal detachment? Following seemingly successful cataract surgery for older HIV+ person is there an increased risk for bad outcome such as retinal detachment or other bad outcme?
 
In a nationwide, population-based cohort study we assessed the risk of cataract surgery in HIV-infected individuals compared with the general population.
 
"HIV-infected individuals have an increased risk of cataract surgery. The risk is mainly associated with immunodeficiency and HAART, but accelerated aging cannot be excluded as part of the possible explanation."

 
As illustrated in Table 3, we found a higher risk of cataract surgery in HIV-infected individuals with a CD4 cell count ≤200 cells/μL before (adjusted IRR, 3.11; 95% CI, 1.26-7.63) or after (adjusted IRR, 4.74; 95% CI, 2.60-8.62) the initiation of HAART (Table 3). In HIV-infected individuals receiving HAART with a CD4 cell count >200 cells/μL, the risk of cataract surgery was still higher than that of the comparison cohort individuals (adjusted IRR, 1.87; 95% CI, 1.46-2.39).
 
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"Patient with prior CMVR may be at risk of reactivation or RD."......
https://iovs.arvojournals.org/article.aspx?articleid=2268154 ----------------------
 
Risk of Cataract Surgery in HIV-Infected Individuals: A Danish Nationwide Population-Based Cohort Study
 
13 October 2011
 
Abstract
Background.
 Premature aging has been suggested a risk factor for early death in patients infected with human immunodeficiency virus (HIV). Therefore, the risk of age-related diseases, such as cataracts, should be increased in this population. In a nationwide, population-based cohort study we assessed the risk of cataract surgery in HIV-infected individuals compared with the general population.
 
Methods. We identified 5315 HIV-infected individuals from a Danish national cohort of HIV-infected individuals and a population-based age- and sex-matched comparison cohort of 53 150 individuals. Data on cataract surgery were obtained from the Danish National Hospital registry. Cumulative incidence curves were constructed. Incidence rate ratios (IRRs) and impact of immunodeficiency, highly active antiretroviral therapy (HAART), and treatment with abacavir, tenofovir, protease inhibitors, and nonnucleoside analogue reverse-transcriptase inhibitors (NNRTIs) were estimated by Poisson regression analyses and adjusted for age, sex, and calendar year.
 
Results. HIV-infected individuals had a higher risk of cataract surgery than the comparison cohort (adjusted IRR, 1.87; 95% confidence interval (CI): 1.50-2.33). The highest risk was found in patients with a CD4 cell count ≤200 cells/μL (adjusted IRR before HAART initiation, 3.11 [95% CI, 1.26-7.63]; adjusted IRR after HAART initiation, 4.74 [95% CI, 2.60-8.62]). In patients not receiving HAART and those receiving HAART with a CD4 cell count >200 cells/mL the adjusted IRRs were 0.60 (95% CI: 0.22-1.61) and 1.87 (95% CI: 1.46-2.39). Treatment with abacavir, tenofovir, protease inhibitors, or NNRTIs did not increase the risk substantially.
 
Conclusions. HIV-infected individuals have an increased risk of cataract surgery. The risk is mainly associated with immunodeficiency and HAART, but accelerated aging cannot be excluded as part of the possible explanation.
 
In conclusion, HIV-infected individuals have a higher risk of cataract surgery than an age- and sex-matched comparison cohort. The risk is associated with a CD4 cell count ≤200 cells/μL and treatment with HAART, but no association with specific antiviral drugs was found. Clinicians should be aware of IRU; however, taking the level of excess risk into consideration, there seems to be no indication for special ophthalmic examinations for cataracts or changes in treatment strategies
 
As illustrated in Table 4, initiation of abacavir (adjusted IRR, 1.23; 95% CI, .75-2.01), tenofovir (adjusted IRR, 1.28; 95% CI, .74-2.21), or PI (adjusted IRR, 1.28; 95% CI, .72-2.29) did not increase the risk of cataract surgery substantially compared with the HAART period before initiation of these antiviral drugs. NNRTI showed a tendency to an increased risk (adjusted IRR, 1.58; 95% CI, .88-2.84), but this was not statistically significant.
 
In a German study from 1994, 101 HIV-infected patients with a median CD4 cell count of 350 cells/μL were prospectively examined for the first ocular symptoms. In 52% of the HIV-infected patients, discrete lens opacities were found by slit-lamp examination, which is why cataract was suggested as a possible early ophthalmological symptom of HIV infection [26]. A cross-sectional study from 2008 retrospectively reviewed the ophthalmic charts of 100 HIV-positive patients with a median age of 31 years (range, 21-80 years) and found that 8% (8/100) had cataracts [27]. However, this study included only patients with a previous diagnosis of ocular disease, and no information on immune status or antiretroviral therapy was given. Moreover, no comparison with the general population was performed in either of the 2 studies.

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DISCUSSION
This study found a higher risk of cataract surgery in HIV-infected individuals compared with a non-HIV-infected age- and sex-matched comparison cohort. Although risk of ocular disease predisposing to cataract is higher in HIV-infected individuals, we found that risk of cataract surgery was not driven only by the high occurrence of such events. The excess risk was highly associated with a CD4 cell count <200 cells/μL and initiation of HAART. No statistical significant excess risk was observed after initiation of abacavir, tenofovir, PIs, or NNRTIs.
 
The strengths of our study include use of a nationwide population-based cohort with a long observation period and complete follow-up. Access to the Danish registries enabled us to identify a population-based age- and sex-matched comparison cohort and to obtain data on study end points from the same data source. Owing to the quality of these data and, furthermore, the availability of electronically collected data on CD4 cell counts and history of antiretroviral treatment from DHCS, selection and information bias was minimized. Because we adjusted the analyses for age, sex, and calendar effects and evaluated the effect of ocular disease predisposing to cataracts, bias due to potential confounding factors was kept to a minimum. We are not aware of other studies with a similar design.
 
Our study has some limitations. Because of the study design, we had no access to clinical data of ophthalmological examinations and thereby information on type or severity of cataracts. We had to rely on hospital registry-based discharge diagnoses. As a result of this, we had to focus on number of patients, rather than number of eyes. We used cataract surgery as a surrogate marker for cataracts, because requirements for registration in Denmark is restricted to hospital contacts. Access to healthcare service in Denmark is quite high, and cataract surgery is performed free of charge in Danish government-owned hospitals and in many private eye clinics. Furthermore, case registration is mandatory if the operation is paid for by the government. However, it cannot be ruled out that a small fraction of cataract operations might not have been identified, but because this potential underregistration is small and nondifferential, it does not affect our estimates of relative risk.
 
Because HIV-infected individuals are intended to be seen in the HIV outpatient clinics 4 times a year and are also closely monitored for signs of opportunistic ocular disease, these individuals might be prone to earlier diagnosis of cataracts and therefore to earlier operation. Although cataract surgery in HIV-infected individuals with extremely low CD4 cell counts may be delayed, low CD4 cell counts in general should not be a reason for postponing such procedures; therefore, this probably does not indicate any larger underestimation of the risk. Our estimates of the impact of immunodeficiency and HAART, however, might still be slightly affected by the uncertainty as to time elapsed from diagnosis to surgery. Finally, we were not able to adjust for some of the risk factors, such as steroid use, diabetes, alcohol intake, and smoking status.
 
In a German study from 1994, 101 HIV-infected patients with a median CD4 cell count of 350 cells/μL were prospectively examined for the first ocular symptoms. In 52% of the HIV-infected patients, discrete lens opacities were found by slit-lamp examination, which is why cataract was suggested as a possible early ophthalmological symptom of HIV infection [26]. A cross-sectional study from 2008 retrospectively reviewed the ophthalmic charts of 100 HIV-positive patients with a median age of 31 years (range, 21-80 years) and found that 8% (8/100) had cataracts [27]. However, this study included only patients with a previous diagnosis of ocular disease, and no information on immune status or antiretroviral therapy was given. Moreover, no comparison with the general population was performed in either of the 2 studies.
 
HIV-infected individuals are prone to ocular disease, such as, for example, uveitis and IRU, which might predispose to cataract [19], This is possibly owing to a higher risk of ocular opportunistic infections. However, Patanapitoon and others have also suggested that HIV can replicate within the eye and cause uveitis [28-30]. In addition, we cannot exclude the possibility that an inflammatory response in the eye that does not cause uveitis might lead to cataracts. Several studies have found a significantly higher risk of cataracts in eyes with IRU [14-18], but the occurrence of IRU seems to vary widely between studies [14, 16, 19, 31, 32]. Goldberg et al studied the long-term visual outcomes in 63 HIV-infected patients (84 eyes) with regressed CMV retinitis who received HAART and found post-HAART cataracts most frequently in eyes with immune recovery and IRU (21/25 eyes [84%]), whereas eyes with immune recovery with no IRU demonstrated the lowest incidence of cataract formation (12/37 [33%]). In addition, cataract formation was observed in 64% (14/22) of the eyes of HIV-infected patients who had never achieved a CD4 cell count of ≥50 cells/μL [33]. This is in accordance with our findings of a higher risk of cataracts in HIV-infected individuals with a CD4 cell count <200 cells/μL. The risk was significantly higher after initiation of HAART, especially in individuals with a CD4 cell count <200 cells/μL, which is why a possible effect of IRU could be suspected. We could not identify individuals with IRU, but analyzing the risk of cataract surgery before ocular disease predisposing to cataract formation, such as uveitis, showed an ∼1.60 times higher risk of cataract surgery.
 
Risk of cataracts has been associated with some medications; the association with steroids is well established [7]. Thorne et al [34] examined 1507 patients (median age, 43 years; range, 15-73 years) with AIDS (3014 eyes) and no recurrent CMV retinitis, of whom ∼80% were taking HAART at the time of enrollment, and found cataracts in 3.6% (110/3013), some due to ocular opportunistic infections other than CMV. A recent Italian study by Accorinti et al [35] retrospectively reviewed the clinical charts of 735 HIV-infected individuals treated with HAART and 838 HIV-infected HAART-naive individuals. They found that the prevalence of uveitis (1.76% vs 0.47%) and that of age-associated ocular diseases, such as cataracts (11.97% vs 1.3%), glaucoma, and diabetic and hypertensive retinopathy, was higher in HIV-infected individuals receiving HAART than in HAART-naive individuals [35]. In conclusion, a possible relation to metabolic alterations induced by HAART, and uveitis induced by immune reconstitution, was suggested. Despite methodological differences in that study, such as lack of adjustments for age and lack of a HIV-negative comparison cohort, these findings correspond with our results, in which the risk of cataract surgery was higher after initiation of HAART. As seen in Table 3, our results indicate that the risk of cataract surgery in the non-HAART period with a CD4 cell count >200 cells/μL was lower than that in the comparison cohort; however, for this period only a few events were observed, and the difference was not statistical significant.
 
Several studies have shown a higher risk of cataracts, occurring at an earlier age, in diabetic patients [9, 11]. Smoking has also consistently been reported as a risk factor [9]. In addition, Nemet et al [10] found a significant association between cataract surgery and cardiovascular disease and its risk factors, such as carotid artery disease, hypertension, peripheral vascular disease, ischemic heart disease, chronic renal failure, hyperlipidemia, diabetes, and smoking. Similar findings were found in a cross-sectional study of 2468 individuals (age range, 60-95 years) by Delcourt et al [36], in which cardiovascular disease (cortical cataract; odds ratio,1.96; 95% CI, 1.22-3.14), smoking, and diabetes of long duration (≥10 years) but not hypertension (cataract surgery; odds ratio, 0.57; 95% CI, .38-.87) was associated with cataracts. Other studies have found that HIV-infected individuals have a higher risk of premature cardiovascular disease as a result of a higher prevalence of conventional cardiovascular risk factors, a direct toxic effect of HAART, and a possible chronic inflammation inducing endothelial dysfunction [37-40]—risk factors that may explain some of the increased risk of cataract surgery we observed. However, HAART could also be an indicator of a population at increased risk of developing illness rather than indicating a toxic effect on the eye induced by HAART. Moreover, accelerated aging in the HIV-infected population cannot be excluded as a possible part of the explanation.
 
In conclusion, HIV-infected individuals have a higher risk of cataract surgery than an age- and sex-matched comparison cohort. The risk is associated with a CD4 cell count ≤200 cells/μL and treatment with HAART, but no association with specific antiviral drugs was found. Clinicians should be aware of IRU; however, taking the level of excess risk into consideration, there seems to be no indication for special ophthalmic examinations for cataracts or changes in treatment strategies.
 
 
 
 
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