Robert K. Hutchins

Loss of Cytomegalovirus-Specific CD4+ T Cell Responses in Human Immunodeficiency Virus Type 1–Infected Patients with High CD4+ T Cell Counts and Recurrent Retinitis

Clinical histories are reported for 2 patients treated with highly active antiretroviral therapy (HAART) who experienced multiple relapses of cytomegalovirus (CMV) retinitis, despite suppression of human immunodeficiency virus type 1 (HIV-1) viremia and improvement in CD4+ T cell counts (to >400 cells/microL). CMV-specific CD4+ T cell immune reconstitution was measured directly, using cytokine flow cytometry, which revealed persistent deficits in CMV-specific CD4+ T cell responses in both patients. CMV-specific T cells constituted 0.14% and 0.05% of the total CD4+ T cell count in these patients, which is significantly lower than the percentages for 34 control subjects (0.6%-46%; CD4+ T cell count range, 7-1039 cells/microL; P=.019). Deficits in pathogen-specific immune responses may persist in some individuals, despite suppression of HIV-1 replication and substantial increases in circulating CD4+ T cells after HAART, and such deficits may be associated with significant morbidity from opportunistic infections.

Retinal endovascular surgery for central retinal vein occlusion: initial experience of four surgeons.

Purpose: The rate and magnitude of spontaneous visual recovery are very poor in central retinal vein occlusion (CRVO). In the first follow-up year, the Central Vein Occlusion Study Group reported that only 6% of eyes recovered ≥3 lines of vision and none recovered ≥8 lines of vision. Retinal endovascular surgery (REVS) is vitrectomy followed by cannulation of retinal vessels with injection of tissue plasminogen activator. After reports of one surgeons experience suggested that the procedure promotes recovery of vision, other surgeons began to offer REVS to their patients. This report discusses the initial experience of four surgeons using REVS to treat CRVO. Methods: In this prospective, consecutive case series, patients with CRVO for >1 week and visual acuity of <20/50 were offered REVS and were followed by the authors. The main outcome measure was recovery of visual acuity. Results: This series represents the initial 25 consecutive REVS cases of the 4 authors (5–7 cases per author). The median CRVO duration was 2 months (mean 2.9, months), and the average preoperative visual acuity was 20/400 (≤20/200 in 80% of cases). Intravitreal triamcinolone acetonide (IVTA) was administered intraoperatively in three cases and at some time postoperatively in six cases. Overall, 18 eyes (72%) recovered ≥3 lines of visual acuity, and 9 (36%) recovered ≥8 lines of vision. Among the surgeons, the rates of ≥3-line visual recovery ranged from 57% to 100%, and the rates of ≥8-line visual recovery ranged from 14% to 71%. Of the 22 eyes that initially underwent REVS without intraoperative IVTA injection, 13 (59%) recovered ≥3 lines of vision and 5 (23%) recovered ≥8 lines of vision. Complications included macular edema (28%), anterior segment or retinal neovascularization (24%), and subsequent cataract surgery (5 [23%] of the 22 preoperatively phakic eyes). One eye had an intraoperative retinal detachment that was treated but recurred 4 months after REVS, and two of the eyes with anterior segment neovascularization developed late-onset traction retinal detachments (at 8 and 13 months after REVS). Conclusion: Although the authors were on the “learning curve” of experience during this series, REVS appears to promote visual recovery far in excess of what would be expected to occur spontaneously, and IVTA injection greatly improved outcomes. We believe that mastery of REVS techniques and the inclusion of IVTA injection may lead to better visual results and lower complication rates.

Chorioretinal lesions in nonfatal cases of West Nile virus infection

OBJECTIVE West Nile virus (WNV) disease is a zoonotic infection with recent outbreaks in the United States. Recent reports have highlighted the intraocular findings associated with WNV disease. We describe the intraocular findings observed in two patients infected by the West Nile virus. DESIGN Observational case reports. METHODS During an outbreak of WNV disease in Southwest Ohio, two patients with an acute onset of a systemic febrile illness accompanied by myalgia, arthralgia, headache, and a maculopapular rash were referred for blurred vision. Complete ophthalmologic examination, fundus photographs, and fluorescein angiograms were obtained on both patients. Both patients underwent serologic testing for viruses and cultures for bacteria, viruses, and fungi. RESULTS Ophthalmologic examination in each patient revealed anterior segment and vitreous inflammatory cells and multiple partially atrophic and partially pigmented chorioretinal lesions clustered in the peripheral fundus. Fundus examination in case 2 also revealed mild disc edema in both eyes. Intracranial pressure as measured by lumbar puncture was borderline elevated. The chorioretinal lesions in both patients showed a striking similarity and appeared hypofluorescent centrally and hyperfluorescent around the edges on a fluorescein angiogram. Serologic testing for the WNV was positive in both patients, and tests for all other bacteria, fungi, and viruses were negative. CONCLUSIONS WNV usually causes mild symptoms, but it occasionally causes neurologic illness with fatal outcome or severe morbidity. We present the cases of two patients with serology-proven WNV disease who developed chorioretinal lesions with a targetlike appearance and iridocyclitis.

Fusarium Endophthalmitis in an Intravenous Drug Abuser

PURPOSE We studied a case in which a patient had unilateral retinal infiltrates and a retinal vasculopathy resembling frosted branch angiitis. He later admitted to injecting cocaine intravenously. METHODS The patient underwent a pars plana vitrectomy and received intravitreal and intravenous amphotericin B. RESULTS The vitreous fluid grew Fusarium dimerium. There was rapid response to the treatment and full recovery of vision. CONCLUSION Fusarium species should be considered as a potential pathogen in intravenous drug abusers with endogenous endophthalmitis and in patients with unilateral frosted branch angiitis.

Ocular Vascular Thrombotic Events: Central Retinal Vein and Central Retinal Artery Occlusions

We prospectively assessed associations of thrombophilia— hypofibrinolysis with central retinal vein occlusion (CRVO) (40 patients) and central retinal artery occlusion (CRAO) (9 patients). We used polymerase chain reaction measures for thrombophilia (factor V Leiden, prothrombin, C677T MTHFR, platelet glycoprotein PlA1/A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). Serologic thrombophilia measures included protein C, protein S (total and free) and antithrombin III, homocysteine, lupus anticoagulant, anticardiolipin antibodies IgG-IgM, and factors VIII and XI. Serologic hypofibrinolysis measures included Lp(a) and plasminogen activator inhibitor activity. For comparison with 40 CRVO and 9 CRAO patients, 80 and 45 race—gender matched controls were studied. The factor V mutation was more common in CRVO (3/40, 8%) than controls (0/79, 0%), P = .036, as was high (>150%) factor VIII (12/40, 30%) versus (4/77, 5%), P = .0002. Low antithrombin III (<80%) was more common in CRVO (5/39, 13%) than in controls (2/73, 3%), P = .049. Homocysteine was high (≥13.5 µmol/L) in 5/39 (13%) CRVO patients versus 2/78 controls (3%), P = .04. Three of 9 CRAO patients (33%) had low (<73%) protein C versus 2/37 controls (5%), P = .044. Two of 9 CRAO patients (22%) had high (≥13.5 µmol/L) homocysteine versus 0/42 controls (0%), P =. 028. Four of 9 CRAO patients had the lupus anticoagulant (44%) versus 4/33 (12%) controls (P = .050). CRVO is associated with familial thrombophilia (factor V Leiden, factor VIII, low antithrombin III, homocysteinemia), and CRAO is associated with familial and acquired thrombophilia (low protein C, homocysteinemia, lupus anticoagulant), providing avenues for thromboprophylaxis, and triggering family screening.

Thrombophilia and retinal vascular occlusion

Purpose The purpose of this research was to assess associations of thrombophilia with central retinal vein occlusion (CRVO), central retinal artery occlusion (CRAO), and amaurosis fugax (AF); to evaluate outcomes of normalizing high homocysteine; and to study CRVO, CRAO, and AF developing in estrogens/estrogen agonists in women subsequently shown to have thrombophilia. Methods Measures of thrombophilia–hypofibrinolysis were obtained in 132 CRVO cases, 15 CRAO cases, and 17 AF cases. Cases were compared to 105 healthy control subjects who did not differ by race or sex and were free of any ophthalmologic disorders. All cardiovascular disease (CVD) risk factors were compared to healthy general populations. Main outcome measures The main outcome measure of this study was thrombophilia. Results CRVO cases were more likely than controls to have high homocysteine (odds ratio [OR] 8.64, 95% confidence intervals [CI]: 1.96–38), high anticardiolipin immunoglobulin M (IgM; OR 6.26, 95% CI: 1.4–28.2), and high Factor VIII (OR 2.47, 95% CI: 1.31–7.9). CRAO-AF cases were more likely than controls to have high homocysteine (OR 14, 95% CI: 2.7–71.6) or the lupus anticoagulant (OR 4.1, 95% CI: 1.3–13.2). In four of 77 women with CRVO (two found to have high homocysteine, two with inherited high Factor XI), CRVO occurred after starting estrogen–progestins, estrogen–testosterone, or estrogen agonists. In one of eight women with CRAO found to have high anticardiolipin antibody IgG, CRAO occurred after starting conjugated estrogens, and AF occurred after starting conjugated estrogens in one of eleven women with AF (inherited protein S deficiency). Therapy for medians of 21 months (CRVO) and 6 months (CRAO-AF) was 5 mg folic acid, 100 mg B6, and 2000 mcg/day B12 normalized homocysteine in 13 of 16 (81%) CRVO cases and all five CRAO-AF cases with pretreatment hyperhomocysteinemia. The CRVO cases had an excess of hypertension; CRAO-AF cases had an excess of type 2 diabetes and hypertension. Conclusion Treatable thrombophilia, hyperhomocysteinemia in particular, is more common in RVO cases than in normal controls. RVO occurs after estrogens or estrogen agonists were administered in women subsequently shown to have thrombophilia.

Outcomes of 25-gauge pars plana vitrectomy in the surgical management of proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE To report outcomes and complications of 25-gauge pars plana vitrectomy (PPV) for patients with complications of proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS Retrospective, interventional, consecutive case series of 174 eyes undergoing primary 25-gauge PPV for PDR from 2006 to 2009. Primary outcomes were visual acuity changes and rates of postoperative complications. RESULTS Visual acuity improved from 20/187 before to 20/69 after surgery (P < .0001). Postoperative vitreous hemorrhage occurred in 38.7% of eyes and 10.4% of all eyes required another PPV for non-clearing vitreous hemorrhage. Complications included limited choroidal effusion (5.2%), rhegmatogenous retinal detachment (4.6%), hypotony, rubeosis, and ocular hypertension (4.1%), neovascular glaucoma (2.3%), hyphema (1.2%), and phthisis bulbi (0.6%). CONCLUSION The authors found 25-gauge PPV to be effective for vitreous removal and membrane dissection. The spectrum and frequency of complications were similar to those reported for 20-gauge PPV for PDR. In the surgical management of PDR, 25-gauge PPV is an alternative.

pseudomonas Aeruginosa Endogenous Endophthalmitis With Choroidal Abscess In A Patient With Cystic Fibrosis

Purpose: To describe the clinical presentation, management, and outcome of a case of endogenous intraocular infection due to Pseudomonas aeruginosa in a patient with cystic fibrosis (CF). Methods: The authors describe a case of an adult patient with CF who developed an intraocular infection by P. aeruginosa. Results: Diagnosis was confirmed by culture of purulent fluid obtained by transcleral incision and drainage. The infection persisted in spite of aggressive surgical intervention including extensive endoresection of the visibly affected retina and choroid and multiple administrations of appropriate intraocular, subconjunctival, and systemic antibiotics. Eventually, the eye became blind and painful and was enucleated. Conclusions: Endogenous intraocular infection by P. aeruginosa can occur in patients with CF who have not undergone lung transplantation. An infection of this type may be impossible to eradicate by aggressive surgical intervention and appropriate antibiotic therapy.

Simultaneous aspergillus endophthalmitis and cytomegalovirus retinitis after kidney transplantation.

We report a case of disseminated and intraocular Aspergillus and cytomegalovirus (CMV) infection in a renal transplant recipient. Aggressive management included reduction of the immunosuppressive medications, systemic and intraocular administration of antifungal agents, treatment with a systemic antiviral drug, and ophthalmic surgery. The clinical and histopathologic features of intraocular Aspergillus and cytomegalovirus infections are discussed. The literature of intraocular mixed opportunistic infections is reviewed.

Analysis of Outcomes for Intravitreal Bevacizumab in the Treatment of Choroidal Neovascularization Secondary to Ocular Histoplasmosis

PURPOSE To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). DESIGN Retrospective, comparative case series. PARTICIPANTS Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010. INTERVENTION Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT). MAIN OUTCOME MEASURES Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals. RESULTS A total of 117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT treatment. For all patients, the average pretreatment logarithm of minimum angle of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB injections per year. There was no significant difference in initial VA, VA at 12 months, VA at 24 months, or number of eyes with a 3-line gain between the IVB monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3 lines or more, and 81.2% (84/104) of subjects had maintained or improved their starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32) follow-up. There was no increase in the proportion of subjects losing 3 lines or more over 3 years of follow-up. CONCLUSIONS There is no significant difference in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The use of IVB alone or in combination with PDT results in significant visual stabilization in the majority of patients with CNV secondary to POHS.