Ординатура / Офтальмология / Английские материалы / Textbook of Vitreoretinal Diseases and Surgery_Natarajan, Hussain_2008

Textbook of Vitreoretinal Diseases and Surgery

FIGURE 22-1: HSV epithelial peripheral keratitis as a presenting feature of HIV in a 23-year-old male

immunocompetent patients. Peripheral location of the geographic or dendritic ulcers may contribute to the delayed healing time. A retrospective cohort study confirmed some, but not all, of the observations made by Young and associates.12

Patients whose corneas are compromised by viral infections, trichiasis, or other insults may develop severe secondary bacterial infections. Treatment is with topical antivirals. The course and presentation of HSV keratitis in HIV infected individuals is no different than in the general population, except for an increased risk of recurrence and a relative lack of stromal inflammation.8

MOLLUSCUM CONTAGIOSUM

Molluscum contagiosum is caused by a DNA virus of the Poxviridae group that produces pearly white, centrally umbilicated skin papules 3 to 5 mm in diameter. The lid margin is involved; a follicular conjunctivitis or keratitis may be seen. In normal hosts, the infection is self-limited, fewer than 10 lesions being present on the face and eyelids. Resolution can sometimes occur within 3 to 12 months of immune reconstitution, although excision, curettage or focal cryotherapy is curative. Immune reconstitution does not necessarily prevent recurrence of molluscum contagiosum, but if new lesions develop, they most likely will be less severe, as seen in immunocompetent individuals8 In the patient with AIDS, lesions have rapid onset, are more numerous, and are larger than in normal hosts and tend to be more resistant to standard therapies.13 Although HIV-infected individuals often suffer from multiple molluscum contagiosum lesions of the eyelids, the ocular surface sequelae that plague affected immunocompetent individuals frequently do not develop, most likely due to an inability to mount an inflammatory reaction.8

KAPOSI’S SARCOMA

Conjunctival involvement occurs in approximately 10-20% of AIDS patients with Kaposi’s sarcoma.8 278 Conjunctival Kaposi’s sarcoma appears as a bright red subconjunctival mass. Small lesions may be mistaken for simple subconjunctival hemorrhages. Kaposi’s sarcoma usually develops in the inferior

Ocular Manifestations of HIV/AIDS

FIGURE 22-5: Pizza pie appearance of CMV retinitis characterized by hemorrhage and retinal necrosis (granular yellow)

may occur first in the peripheral retina; therefore thorough examination of the fundus by indirect ophthalmoscopy is important in the management of AIDS patients.

Active retinitis has three general patterns. The commonest classic lesion is the hemorrhagic, 15 Large areas of retinal hemorrhage on a background of whitened, necrotic retina “crumbled cheese and ketchup” or “pizza pie appearance” (Figure 22-5).

Another description is a Brush fire appearance which is seen as a yellow-white margin of slowly advancing retinitis at the border of atrophic retina. Granular retinal necrosis is found in the periphery which manifests as focal white granular lesions without associated hemorrhage. Necrotic stage - end result of all patterns of active retinitis is the progression to necrosis. Retinal tears or holes can develop in these areas. There is relatively little inflammatory reaction to CMV infection of the retina. The overlying vitreous remains remarkably clear. With extensive hemorrhage, the appearance may simulate a central retinal vein occlusion or branch vein occlusion. Primary CMV involvement of the optic nerve results in a yellow-white disc with small hemorrhages. CMV retinopathy is relentlessly progressive; spontaneous resolution has not been observed. Individual foci coalesce and spread to involve the entire retina over a period of several months. CMV retinitis severely impairs the quality of remaining life in AIDS patients, 40 percent of those affected losing central vision in both eyes by the time of death. The introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of cytomegalovirus (CMV) retinitis, but has not eliminated new cases altogether.20

Treatment

Treatment strategies for CMV retinitis have evolved over the past decade. Current issues of importance include choice of initial anti-CMV drugs; time at which anti-CMV drug treatment is discontinued in patients who achieve immune recovery; strategies for monitoring patients at risk for disease reactivation; and management of complications (retinal detachment, immune recovery uveitis). Table 281 22-2 summarizes ganciclovir for the treatment of CMV retinitis.

Textbook of Vitreoretinal Diseases and Surgery

TABLE 22-2: Ganciclovir in CMV retinitis

Adult Dose IV induction: 5-7.5 mg/kg/d for 2-3 wk

IV maintenance: 5 mg/kg/d 5 d/wk

Oral maintenance dose: 1000 mg tid

Intravitreal implant is an effective long-term alternative but a costly option.

Pediatric Dose 5 mg/kg once qd

Decrease dose for severe renal failure, neutropenia, or thrombocytopenia

A dose dependent increase in neutropenia exists

Reactivation of retinitis while on maintenance dose will require reinduction

Adverse effects.

Myelosuppressive; neutropenia (40%),Thrombocytopenia (18%);Anemia;Infertility; rash

Monitor CBC/platelets q2d during induction, then weekly

Patients treated with ganciclovir often initially feel better as CMV activity in the brain, lungs, liver, kidneys, gastrointestinal tract, and adrenal glands is also inhibited. A physician or infectious disease specialist should coordinate medical care. Ophthalmic assessment is required on a regular basis, with frequency dependent on existence of CMV retinitis and on CD4 count.

Intravitreal injections of ganciclovir (catheterless therapy) has been successful in inhibiting CMV retinitis. A dose of 2000-5000 mcg21 ganciclovir in 0.01ml sterile water is given through the pars plana with a 27or 30-gauge needle 1 to 2 times/wk. Potential problems include endophthalmitis, retinal detachment, and vitreous hemorrhage. On initiating HAART, patients with CMV retinitis may enjoy significant recovery in CD4+ counts and sustained retinitis quiescence without specific anti-CMV therapy. Intravitreal ganciclovir injections seem well suited to offer effective CMV control during temporary periods of decreased CD4+ counts while awaiting HAART-mediated immune system reconstitution.22 This therapy has become a standard treatment in most centers because of cost considerations. Acyclovir is not effective in treating established CMV retinitis. Other treatment options for CMV infections of the eye are intravenous and/or intravitreal Foscarnet and Cidofovir. Intravitreal Fomvirsen a novel antisense medication is also a lesser known alternative that has fewer roles in extraocular CMV infection. Intravitreous Fomvirsen is well tolerated with an acceptable safety profile. Common adverse ocular were anterior chamber inflammation and increased intraocular pressure.23

Vitreoretinal Surgery in CMV Retinitis

Vitreoretinal Surgery in CMV retinitis associated retinal detachment is indicated in 5-50% of patients with CMV retinitis. The risk factors24 are peripheral retinal involvement greater than 25% area, the presence of active retinitis, older age; lower CD4 cell counts and presence of multiple small holes in several areas of the retina are often responsible for the retinal detachment. These occur at the junction of healthy and necrotic retina. Multiple or single holes, as well as micro holes, were observed in areas of retinal necrosis leading to complex retinal detachments. Strong vitreoretinal adherences in young AIDS patients, associated with chronic inflammation, are important elements in the pathophysiology of retinal detachment in AIDS patients24. Primary repair with vitrectomy, air-fluid exchange, endolaser, and silicone oil endotamponade has improved surgical outcome.

CMV retinitis is an indolent infection spreading slowly over the course of many weeks or months 282 to eventually involve the entire retina. Without treatment, vision is usually lost because of optic nerve involvement, spread of the lesions into the macula with macular necrosis, or retinal detachment.

Textbook of Vitreoretinal Diseases and Surgery

OCULAR TUBERCULOSIS (TB) IN AIDS

Ocular TB in AIDS is relatively rare and can occur even at CD4+ cell counts greater than 200 cells/ microlitre. Babu RB et al29 have reported various presentations of ocular TB that included choroidal granulomas, subretina abscess worsening to panophthalmitis, conjunctival tuberculosis, and panophthalmitis.1.95% cases of AIDS had ocular tuberculosis in their series. It is important to diagnose and treat ocular tuberculosis in AIDS patients as immune recovery tuberculosis can destroy eye when HAART is instituted. Diagnosis is by clinical appearance and presence of pulmonary or extrapulmonary tuberculosis, along with demonstration of mycobacterium tuberculosis MPB-64 genome by PCR study of ocular specimens. Treatment is a complete 9-12 months course of antituberculous therapy (ATT). HAART should be instituted 2-3 months after instituting ATT.

OCULAR SYPHILIS IN AIDS

Syphilis increases the risk of a coinfection of HIV to 5 to 7 times that of the general population.30 All patients presenting with syphilis should be offered HIV testing and all HIV-positive patients should be regularly screened for syphilis.31 Syphilis agent may enhance the transmission of the other, probably through increased incidence of genital ulcers. Syphilis serology may be negative when patients present with inflamed eyes and co-infection with syphilis and HIV.

The testing titers are also higher than those observed in immunointact patients, and syphilis tends to progress much more rapidly to the tertiary stage in these patients. The eyes and visual system can be affected in many different ways by syphilis but none of the signs are pathognemonic. All structures of the eye may be affected but the commonest manifestation is uveitis (intraocular inflammation).32 Uveitis can occur at all stages of syphilis including primary infection33 and may spontaneously resolve but the relapse rate is high without treatment.

Patients with posterior uveitis may have vitritis, focal retinitis, chorioretinitis periphlebitis, retinal haemorrhages, papillitis, and exudative retinal detachments. Many other signs of intraocular involvement may be seen including optic neuritis, neuroretinitis, arterial and venous occlusion. Most patients recover well with penicillin treatment but visual loss can occur from macular edema and retinal ischemia from the endarteritis.36 However, not all ocular syphilis can be cured with neurosyphilis regimens and many more will relapse with less intense regimens.35 Penicillin in megadose (Aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4 h or continuous infusion, for 10–14 days.) remains the antibiotic of first choice. Alternatives are Doxycycline 200 mg BD for 28 days or Amoxycillin 2 g TDS plus probenecid 500 mg QDS for 14 days.37

Other Rarer Intraocular Infections

PNEUMOCYTIS CARINII CHOROIDITIS

Pneumocystis carinii pneumonia (PCP) is one of the most common opportunistic infections seen in patients with AIDS. It is also the most common cause of death in these patients. Macher and coworkers reported the first reliable evidence of Pneumocystis infection of the choroid.38 Subsequently there were a few more reports.39-41 Diagnosis of choroidal involvement is extremely important, since the presence of Pneumocystis choroiditis is evidence of life-threatening systemic infection. Treatment should be instituted and may include oral trimethoprim-sulfamethoxazole or IV pentamidine. The

284 choroidal lesions will usually respond to therapy. Other infections known to occur are cryptococcal choroiditis, fungal retinitis and chorioretinitis and atypical mycobacterial infections.

Textbook of Vitreoretinal Diseases and Surgery

TABLE 22-3: Differentiating features of three types of viral retinitis in AIDS

Adapted from: Ocular lesions associated with AIDS in india, practical guidelines for diagnosis and management, Dr. Jyotirmay Biswas Sankara Nethralaya, Chennai

multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antiviral drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS.

Neuro-ophthalmic Complications of Intracranial Disease

Neuro-ophthalmic problems,45.46 including optic neuropathies, motility disturbances, and visual field defects, are an important and common part of the AIDS spectrum. However, diverse and challenging to the clinician, they may be the initial presentation of HIV infection. While opportunistic infections and neoplasms comprise the major source of neuro-ophthalmic problems, HIV itself may also be cause of neuropathy due to various mechanisms. Coexisting infections and neoplastic processes in the eye and brain create a diagnostic challenge for the clinician. Although tuberculous meningitis is the most common neuro-infection, with the advent of the Acquired Immunodeficiency Syndrome

286 (AIDS) pandemic, more and more cases of fungal meningitis especially due to cryptococcal infection are seen in clinical practice. Cryptococcal meningitis47 has emerged as a leading cause of infectious

Ocular Manifestations of HIV/AIDS

morbidity and mortality in patients with AIDS. Papilledema due to cryptococcal meningitis is the commonest neurophthalmic lesion noted in AIDS patients. Other manifestations include cranial nerve palsies, optic neuritis, optic atrophy and pupillary abnormalities.

Central nervous system opportunistic infections (OIs)49 lesions like toxoplasmic encephalitis, lymphoma, progressive multifocal leucoencephalopathy (PML) and fungal granulomas can also produce peculiar neurophthalmic features in AIDS patients. These entities may present with ophthalmic symptoms and, the diagnosis of these entities is made with noninvasive methods. Imaging studies, especially magnetic resonance imaging, are very useful for the diagnosis of tuberculous meningitis, toxoplasmic encephalitis and PML.

Once HAART is initiated, some patients can develop a clinical worsening of some CNS OIs with or without atypical neuroimaging manifestations. This paradoxical worsening is known as the immune reconstitution inflammatory syndrome (IRIS) and it results from reconstitution of the immune system’s ability to recognize pathogens/antigens in patients with prior OIs and low CD4+ T-cell counts. In this context, IRIS can be seen in patients with CNS cryptococcosis, tuberculosis, or PML.49 On the other hand, HAART-induced immune reconstitution can improve the prognosis of some untreatable diseases such as PML, and can allow maintenance therapy of some CNS-OI to be safely discontinued in patients with high and sustained CD4+ T-cell response. Therefore it is important to monitor these patients for worsening or improvement of ocular complication during HAART.

Newer Entities

IMMUNE RECOVERY UVEITIS SYNDROME

Immune recovery uveitis (IRU) is an intraocular inflammatory disorder originally described in individuals with human immunodeficiency virus (HIV) and inactive cytomegalovirus retinitis following highly active antiretroviral therapy.50 Immune recovery uveitis (IRU) is characterized by vitritis and posterior segment complications thereof, most commonly cystoid macular edema (CME) and/or epiretinal membrane formation. Preretinal neovascularization, papillitis, proliferative vitreoretinopathy, and anterior segment inflammation, sometimes with iris synechiae and cataract, have been reported in a smaller number of cases. Symptoms typically include floaters and/or moderate to severe vision loss.50-56 Risk factors include larger retinal involvement due to CMV retinitis and intravitreal use of Cidofovir. Eyes with IRU respond favorably to antiinflammatory therapy in the form of oral topical or periocular steroids under close supervision without reactivation of retinitis54. CMV retinitis is usually inactive in cases of IRU due to an improvement in immunity. IRU can occur in eyes with active CMV retinitis, particularly at the onset of the inflammation. More aggressive anti-CMV drug therapy, especially during the initial period of immune recovery, seems to be associated with a reduced risk of IRU, presumably because of a decreased antigen load.57

From a practical standpoint, patients who were never on HAART found to have CMV retinitis should be treated aggressively with anti-CMV drugs, and treatment should be continued through the period during which immune recovery is achieved, before considering discontinuation of treatment.58

NEOPLASMS IN HIV

Squamous Cell Carcinoma

Squamous cell carcinoma occurs at an earlier age in HIV-infected individuals, and is often more 287 aggressive, than in immunocompetent individuals.59 Squamous cell carcinoma has been linked to