Purpose
To assess the prevalence of proliferative vitreoretinopathy (PVR) and prognosis of cytomegalovirus (CMV) retinitis–related retinal detachment (RD) surgery in the era of highly active antiretroviral therapy (HAART).
Design
Retrospective interventional cohort study.
Methods
Thirty-five human immunodeficiency virus (HIV)-positive patients with CMV retinitis–related RD who underwent surgical repair were assessed for PVR, CD4-positive T cell counts, and use of HAART. Main outcome measures included anatomic and functional outcomes of RD surgery as well as the presence of PVR and CD4-positive T cell counts.
Results
PVR was present in 10 of 35 patients (29%) at the time of the first surgery. The presence of PVR was associated with worse preoperative and postoperative visual acuity ( P = .017 and P = .009, respectively), with the CD4-positive T cell counts above 200 cells/μL ( P = .054), and with a longer interval between the diagnosis of RD and surgery ( P = .025). The odds ratio for development of PVR in patients with CD4-positive T cells above 200 cells/μL was 11.3 (95% confidence interval 1.01-125). PVR was not associated with age, gender, or duration of HIV infection. Anatomic reattachment was obtained in 31 patients (89%), though the functional outcomes were limited. The central location of CMV retinitis was associated with postoperative visual acuity (VA) of less than 0.1 ( P = .000). Postoperative logMAR VA was associated with preoperative logMAR VA ( P < .001) and development of PVR ( P = .009).
Conclusion
PVR was present in 29% of CMV retinitis–related RD and was associated with higher CD4-positive T cell counts and longer interval between the diagnosis of RD and surgery.
Cytomegalovirus (CMV) retinitis is the most frequent intraocular infection observed in human immunodeficiency virus (HIV)-infected patients. In the era before highly active antiretroviral therapy (HAART), CMV retinitis developed in about 30% of HIV-positive individuals; more than 30% of those surviving for longer than 1 year after the onset of CMV also developed rhegmatogenous retinal detachment (RD). Since the life expectancy in patients with CMV retinitis was very limited, the long-time prognosis of RD surgery in the pre-HAART era was not known. In the HAART era, the risk of CMV infection and subsequent RD substantially decreased, which is not only attributable to the decreased numbers of patients affected by CMV retinitis but also to its earlier and better treatment. Overall, the rate of RD in the HAART era is 0.06/person-years, versus 0.33/person-years in the pre-HAART period. However, if the CD4-positive T cell counts reach the region of less than 50 cells/μL, then the risk of developing RD is similar to that of the pre-HAART era (0.30/person-years). In general, in the HAART era, the realization of anatomic reattachment following RD surgery is satisfactory, though the achievement of successful visual outcome is limited as the majority of affected eyes remain visually impaired or blind.
In this report, we describe the prognosis and complications of the RD surgery in HIV-positive patients with previous CMV retinitis and report on proliferative vitreoretinopathy (PVR) development in this population.
Methods
We conducted a retrospective analysis of the medical records of 37 consecutive HIV-positive patients with CMV retinitis–related RD who underwent surgical repair between September 2004 and March 2009 in Chiang Mai University Hospital. Two patients had long-standing vitreous hemorrhage in their affected eyes and were therefore excluded from the final analysis, since the presence of vitreous hemorrhage is significantly associated with the development of PVR.
The newly diagnosed patients with HIV with CMV-related RD were referred to the specialist in infectious diseases and had to agree to start the HAART treatment. Thirty-three patients (33/35, 94%) had lost useful vision in their other eyes (31 because of CMV retinitis with or without RD, 1 because of trauma, and the remaining patient because of congenital blindness of unknown origin). Pars plana vitrectomy (PPV) was employed as the usual procedure for the repair of RD. All operations were performed by 3 surgeons (P.K., D.P., J.C.) using a similar technique including PPV, removal of the posterior hyaloid membrane with relief of all retinal traction, endodrainage of subretinal fluid via intended retinotomy, and fluid-air exchange. Endolaser or cryoretinopexy were used around any retinal breaks and the retinotomy site. For intraocular tamponade, either silicone oil or perfluoropropane (C3F8) were used. One patient underwent pneumatic retinopexy with C3F8 solely because of very limited RD.
The medical files of patients were reviewed and the following data registered: age and gender of patients, treatment modalities and their timing, CD4-positive T cell counts at the time of surgery, preoperative and postoperative VA, and all complications. For the classification of PVR, we used the 1991 classification and severe PVR was defined as PVR grade C. Complete anatomic success was considered if the whole retina was reattached after the operation, and the term “partial success” was used if the retina including the macular area was attached, though the peripheral inferior retina was still detached. Average postoperative follow-up was 13 months (median 10, range 1-58 months). Before analyses, visual acuity (VA) was always transformed to a logarithm of the minimal angle of resolution (logMAR). For data presentation, the results were converted back to Snellen VA.
We used SSPS 15.0 for Windows (SPSS Inc, Chicago, Illinois, USA) for statistical analyses. To find the association between the PVR and CD4-positive T cell counts, corrected for interval between the diagnosis RD and surgery, the Mantel-Haenszel common odds ratio was calculated.
Results
General characteristics of our patients are given in Table 1 . The male-to-female ratio was 20:15 and the average age at the time of the diagnosis of RD was 37 years (male patients 38 years, female patients 35 years). The median interval between the diagnosis of RD and the time of surgery was 2 months (range < 1 week to 27 months). Before the development of RD, zone 1 CMV retinitis was present in 14 patients. Total RD was present in 20 patients and partial in 15; however, attached macula was preoperatively noted only in 4 cases. Median CD4-positive T cell count in our series was 241 cells/μL (average 298 cells/μL, range 8 to 884). CD4-positive T cell counts of less than 200 cells/μL were present in 13 of 35 patients (37%).
| Characteristic | Total (n = 35) | PVR (n = 10) | No PVR (n = 25) | P Value |
|---|---|---|---|---|
| Median age (years) | 38 | 39.5 | 38 | .609 a |
| Male-to-female ratio | 20:15 | 5:5 | 15:10 | .712 |
| Median interval between RRD and surgery (months) | 2 | 2.5 | 1 | .021 a |
| CD4 counts ≤ 200 cells/μL | 13 (37%) | 1 (10%) | 12 (48%) | .054 |
| Preoperative visual acuity ≥0.1 | 12 (34%) | 0 | 12 (48%) | .007 |
a Mann-Whitney U test; in all other calculations Fisher exact test was used.
Twenty-nine patients started HAART medication around the onset of their CMV retinitis, 5 patients received HAART after the diagnosis of CMV retinitis but before the development of RD, and only 1 patient did not receive HAART before surgery. CMV retinitis was treated in 23 of 35 patients (66%) with intravitreal ganciclovir injections for various periods of time before the onset of RD (remaining 12 patients were concurrently diagnosed with CMV retinitis/scars and RD) and 32 patients had inactive CMV with scarified lesions before the surgical intervention. Only 3 patients had to undergo the operation with still-active CMV retinitis. One of these patients started his intravitreal ganciclovir injections and HAART medication 4 months before surgery; his CD4-positive T cell count rose to 231 cells/μL and immune recovery uveitis (IRU) developed together with severe PVR. This patient was the only one with IRU in our series; the signs typical of IRU were absent in all the other patients included. The second patient had very low CD4-positive T cell counts (8 cells/μL) despite receiving HAART for longer than 6 months. In the remaining patient the diagnosis of HIV, CMV, and RD was made concurrently; his CD4-positive T cell counts were low (10 cells/μL) and PVR did not develop. He was the only patient who did not receive HAART before surgery.
PPV with silicone oil tamponade was employed in 27 of 35 patients (77%), PPV with C3F8 in 4 patients (11%), and pneumatic retinopexy with C3F8 in 1 patient (3%). For the remaining 3 patients surgery was aborted as the reattachment could not be accomplished (all had PVR grade C). In the silicone oil group, anatomic success was achieved in 26 of 27 patients (96%). Out of 4 patients with C3F8 tamponade, 2 needed a second surgical intervention with silicone oil injection for complete retinal reattachment. Additional operations in the silicone oil group were performed in 13 patients (6 cataract surgery, 4 combined cataract surgery and silicone oil removal, 1 silicone oil removal, and 2 injection of silicone oil).
At the time of the first surgery, PVR was present in 10 of 35 patients (29%; PVR grade C in 4, or 11%). The presence of PVR was associated with poor preoperative and postoperative VA and exhibited a significant association with the CD4-positive T cell counts above 200 cells/μL ( P = .054, Fisher exact test) and a longer interval between the diagnosis of RD and time of surgery ( P = .02, Mann-Whitney U test) as well as with a lack of accomplishment of anatomic success ( P = .004, Fisher exact test). The odds ratio for the development of PVR in patients with CD4-positive T cells above 200 cells/μL, corrected for interval between the diagnosis of RD and the time of surgery, was 11.3 (95% confidence interval 1.01-125). PVR development was not associated with other characteristics such as age and gender.
Anatomic success was achieved in 31 of 35 patients (89%; complete in 27 and partial in 4) and was strongly associated with the absence of PVR ( P = .004; Fisher exact test), but not with having HAART at the time of CMV retinitis ( P = 1.0, Fisher exact test) or the interval between the diagnosis of RD and surgery ( P = .560, Mann-Whitney U test). Although anatomic success was obtained in the majority of patients, the functional outcome was limited (VA of at least 0.1 was achieved in 19/35, 54%; Table 2 ). The improvement of more than 2 lines occurred in 3 of 10 PVR eyes (30%) and 10 of 25 non-PVR eyes (40%) ( P = .709, Fisher exact test). Postoperative VA of ≤ 0.1 was strongly associated with zone 1 CMV retinitis (0/13 vs 14/16; P = .0000, Fisher exact test); less strong association was found with the number of eyes with detached macula prior to surgery (4/15 vs 0/20; P = .02, Fisher exact test) and no association with preoperative lens extraction (1/15 vs 1/20; P = 1.0, Fisher exact test). Postoperative logMAR VA (1 and 3 months follow-up) was associated with preoperative logMAR VA ( P < .001 for both, Pearson correlation) and the absence of PVR ( P = .009, Mann-Whitney U test) but not with other characteristics including age, gender, the interval between CMV retinitis and RD, the interval between the diagnosis of RD and the time of surgery, or the CD4-positive T cell count at the time of surgery.
