Ocular manifestation of hiv

OCULAR MANIFESTATION OF HIV INFECTION

1. Ocular Manifestations of HIV Infection DR MD SHAHID MANZOOR AMUIO, ALIGARH

2. INTRODUCTION Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS) is a disease of the human immune system caused by infection with human immunodeficiency virus (HIV). leads to gradual decrease in CD4+ T lymphocytes causing subsequent opportunistic infections and neoplasia. 70-75% of patients infected with HIV will develop some form of ocular involvement.

3. Ocular manifestations of HIV/AIDS Direct infection by HIV, Opportunistic infections Neoplasia and Drug related

4. Ocular manifestations correlating with immune status and stage of HIV infection

5. A ) ADNEXAL MANIFESTATIONS B) ANTERIOR SEGMENT MANIFESTATION C) POSTERIOR SEGMENT MANIFESTATIONS D) NEURO-OPHTHALMIC MANIFESTATIONS E) ORBITAL MANIFESTATIONS F) DRUG-RELATED OCULAR TOXICITY IN HIV- INFECTED PATIENTS

6. A) Adnexal Manifestations 1) Herpes zoster ophthalmicus (HZO) 2) Kaposi sarcoma 3) Molluscum contagiosum 4) Conjunctival microvasculopathy

7. 1) Herpes Zoster Ophthalmicus 5-15% of HIV patients. Reactivation of a latent infection by VZV in the dorsal root of trigeminal nerve . Manifests with a painful maculo - papulo -vesicular rash . Involves the upper lid and does not cross the midline. Keratitis , scleritis , uveitis , retinitis , or cns involvement Cranial nerve palsies

8. Herpes Zoster Ophthalmicus

9. Herpes Zoster Ophthalmicus Intravenous acyclovir 10 mg/kg 3 times per day for 7 days, followed by oral acyclovir 800 mg to 1 g 5 times per day for an additional 7 days. This regimen is most effective when started within 72 hours of onset of the vesicular lesions. This treatment reduces the frequency of recurrences.

10. 2) Kaposi sarcoma 25% of HIV patients. Human herpes virus type 8 Mesenchymal -derived vascular neoplasm. Manifests with a violet-brown , non-tender nodule. Eyelid and conjunctival Kaposi sarcoma tend to mimic chalazion and localized subconjunctival hemorrhage , respectively. It can progress rapidly to other sites such as the gastrointestinal tract and CNS Complications of ocular Kaposi sarcoma include trichiasis and entropion formation. .

11. Kaposi sarcoma

12. Kaposi sarcoma

13. Kaposi sarcoma Radiation therapy Intralesional chemotherapy with vinblastine , alpha interferon, and liposomal daunorubicin . Surgical excision of the tumor .

14. 3) Molluscum contagiosum 20% of HIV patients It is a highly contagious dermatitis caused by DNA poxvirus, and it may affect mucous membranes as well as skin. Manifests with multiple, small, painless, umbilicated lesions which produce a waxy discharge when pressured. A self-limiting disease with spontaneous resolution taking months to years.

15. Molluscum contagiosum

16. Molluscum contagiosum

17. Molluscum contagiosum Molluscum contagiosum lesions of the skin can be treated with Excision (with or without curettage) Cryotherapy Topical agents- phenol and trichloroacetic acid.

18. 4) Conjunctival microvasculopathy 70 - 80% of HIV patients Increased plasma viscosity immune-complex deposition are believed to be involved and Direct infection of the conjunctival vascular endothelium by HIV. These changes include segmental vascular dilation and narrowing, microaneurysm formation, and appearance of comma-shaped vascular fragments.

19. Conjunctival microvasculopathy

20. B) Anterior Segment Manifestations More than 50% of HIV-positive patients Common symptoms include irritation, pain, photophobia, redness and decreased vision 1) Keratoconjunctivitis sicca 2) Keratitis 3) Iridocyclitis

21. 1) Keratoconjunctivitis sicca 10-20% of patients who are HIV positive. The etiology is related to HIV-mediated inflammation and damage of the accessory and major lacrimal glands. Patients complain of burning uncomfortable red eyes. Artificial tears and lubricating ointment.

22. Keratoconjunctivitis sicca

23. 2) Infectious keratitis Main etiology – Viral (VZV and HSV )- most frequent but less severe Bacterial and less frequent but more severe. Fungal keratitis The most common fungal organism is Candida, especially in intravenous drug users and Fusarium and Aspergillus species .

24. VZV HSV Dermatomal distribution Complete Incomplete Pain Increased less Scarring of skin Frequent Rare Postherpetic neuralgia Frequent Rare Dendrites Small without central ulceration or terminal bulbs Large with central ulceration and terminal bulbs Iris atrophy Sectoral Patchy, with no sectoral Recurrent lytic epithelial keratitis No recurrent Frequent recurrent

25. Varicella -zoster virus keratitis Recommended treatment is Oral acyclovir 800 mg 5 times per day or famciclovir 125-500 mg 3-5 times per day. Chronic treatment may be required for VZV keratitis . This usually minimizes symptoms and shortens the duration of viral shedding. Severe disciform stromal keratitis - treated with topical corticosteroids.

26. Herpes simplex virus keratitis Debridement of HSV epithelial keratitis with a dry cotton-tipped applicator or a cellulose sponge can hasten resolution and decrease the load of infectious virus and viral antigens. Medical treatment includes acyclovir topical 3% ointment 5 times daily for 14 days or oral dosage form 400 mg 5 times daily for 7 days; or famciclovir 500 mg by mouth 3 times daily for 7 days. HSV neurotrophic keratopathy is a condition that should be managed with nonpreserved lubricants, eyelid patching, bandage contact lenses, and sometimes autologous serum and nerve growth factor.

27. 3) Iridocyclitis The etiology of iridocyclitis in HIV-positive patients includes sequelae of retinitis, retinochoroiditis , and drug toxicity ( rifabutin , cidofovir ), secondary to direct toxic effect upon the non-pigmented epithelium of the ciliary body. Mild iridocyclitis associated with viral retinitis due to CMV,HSV, VZV. Severe, seen in association with ocular toxoplasmosis, tuberculosis, syphilis, or bacterial or fungal retinitis.

28. Treatment Topical corticosteroid drops are used frequently but with extreme caution and with proper antimicrobial coverage when infection is suspected. If toxicity from the medication is suspected, the dose should be tapered or the causative agent should be discontinued.

29. C) Posterior Segment Manifestations Posterior segment structures involved in HIV-positive patients include the retina, choroid, and optic nerve head. 50% of patients who are HIV positive. Symptoms are floaters, flashing lights, visual field defect, and decreased visual acuity. Presence of an afferent pupillary defect strongly suggests significant retinal or optic nerve involvement. Diagnoses often are based on clinical evidence seen on funduscopic examinations.

30. Posterior Segment Manifestations 1) HIV retinopathy 2) HIV-related retinochoroiditis

31. 1) HIV retinopathy 50-70% of HIV-infected patients Arteriolar occlusion in HIV retinal microvasculopathy leads to interruption of the axoplasmic flow and the subsequent accumulations of axoplasmic debris, which manifests as cotton-wool spots. Increased plasma viscosity, immune-complex deposition, and a direct cytopathic effect of the virus on the retinal vascular endothelium are believed to be involved.

32. asymptomatic and transient, but it may contribute to the optic nerve atrophy seen in many of the patients. Common findings may include the following: Cotton-wool spots Intraretinal hemorrhages Roth spots (white- centered hemorrhages ) Retinal microaneurysms No treatment is indicated for HIV retinopathy. These patients require observation only.

33. 2) HIV-related retinochoroiditis Viruses are the MC CMV , VZV and, less commonly HSV . Bacterial causes include Mycobacterium tuberculosis and Treponema pallidum (syphilis). Parasitic causes include Toxoplasma gondii and Pneumocystis jiroveci Fungal causes include Candida, Cryptococcus neoformans , and Histoplasma capsulatum , as well as, Sporothrix , and Aspergillus species. .

34. Cytomegalovirus retinitis Acute Retinal Necrosis Progressive Outer Retinal Necrosis ( Varicella -Zoster Retinitis) Toxoplasma Retinochoroiditis Tuberculosis.

35. Cytomegalovirus retinitis M ost common cause of intraocular infection U sually in CD 4 < 50 /microlitre Painless , progressive loss of vision It presents with a wide range of clinical appearances, from cotton wool to confluent areas of full thickness retinal necrosis. Infection spreads centrifugally from that focus with advancement of lesion borders toward the fovea like “brushfire” pattern at a median rate of 24 μ m/day.

36. The retinitis begins as small, white perivascular retinal infiltrates .

37. The classic lesion is a hemorrhagic necrotizing retinitis that follows the retinal vasculature

38. Fluffy retinal infiltrates and necrosis are associated with scattered hemorrhages , this creates what has been called the "scrambled eggs and ketchup“or ‘pizza pie appearance of severe CMVR

39. TREATMENT Oral Valganciclovir . Oral ,Intravenous, and Intravitreal ganciclovir . Intravenous and Intravitreal Foscarnet or combined intravenous Ganciclovir and Foscarnet Intravenous Cidofovir Inhibiting CMV DNA polymerase.

40. Cytomegalovirus retinitis Valganciclovir is the drug of choice for the treatment of CMV retinitis. Induction is 900 mg twice a day and then 900 mg once a day for maintenance. For ganciclovir , start induction with 5 mg/kg IV every 12 hours for 14 days, then change to a maintenance IV dose of 5 mg/kg/day for 7 days. myelosuppression

41. Cytomegalovirus retinitis Foscarnet Induction with 60 mg/kg IV every 8 hours for 14 days. Maintenance IV dose of 90-120 mg/kg/day. Hydration with 1000 mL of isotonic sodium chloride solution is recommended because of renal toxicity associated with foscarnet .

42. Cytomegalovirus retinitis Cidofovir Induction dose - 5 mg/kg IV over 1 hour once weekly for 2 weeks. Maintenance dose - 5 mg/kg over 1 hour once every other week. Renal toxicity, Iritis and Ocular hypotony .

43. Acute Retinal Necrosis It is a fulminant retinal vaso -occlusive necrotizing retinitis , usually due to Varicella -Zoster infection, can also be caused by Herpes Simplex virus or Cytomegalovirus. The retina shows small, necrotic yellowish lesions in the periphery, which rapidly spread into a larger confluent white area, most often involving the entire peripheral retina, and then progress toward the posterior pole. Optic neuritis and retinal detachment are frequent complications.

44. Acute Retinal Necrosis

45. Acute retinal necrosis Acute retinal necrosis (ARN) frequently is complicated by anterior uveitis , retinal and choroidal vasculitis , vitritis , and papillitis . Episcleritis , scleritis , or optic neuropathy. are treated with high doses of intravenous aciclovir or famciclovir , combined with laser treatment to prevent retinal detachment

46. Progressive Outer Retinal Necrosis ( Varicella -Zoster Retinitis) It is is a rapidly progressive, necrotizing retinitis caused by Varicella Zoster virus, without vitritis or retinal vasculitis . The retina shows typically a white lesion (multifocal, deep to the retina, opaque, and patchy) with no haemorrhages or exudates. Typically, the lesions start from the posterior pole and spread with extreme rapidity to involve the entire retina.

47. Progressive Outer Retinal Necrosis ( Varicella -Zoster Retinitis)

48. Progressive Outer Retinal Necrosis ( Varicella -Zoster Retinitis)

49. Progressive outer retinal necrosis Treatment is often unsatisfactory and usually requires combination of Ganciclovir and Aciclovir . The prognosis is very poor and retinal detachment is common.

50. TUBERCULOSIS The most common ocular manifestation is anterior uveitis and disseminated choroiditis . Manifests as areas of necrosis surrounded by mononuclear and giant cells. unifocal or multifocal yellowish, grayish , or whitish choroiditis , mostly in the posterior pole.

51. Patients should be given isoniazid (INH) 300 mg orally daily, rifampin 600 mg orally daily, and pyrazinamide 25-35 mg/kg orally daily for 2 months; then, continue with INH and rifampin for an additional 7 months. Drug resistance is most common with streptomycin and INH; however, this may be minimized by the use of multiple bactericidal antituberculous drugs. Pyridoxine 25 mg orally daily usually is added to the regimen to prevent peripheral neuritis.

52. Toxoplasma Retinochoroiditis The usual ocular lesion of toxoplasmosis is a focal necrotizing retinitis, with white infiltration and surrounding retinal edema . Unlike in immunocompetent patients, HIV infected patients often have bilateral and multifocal disease associated with anterior uveitis and vitritis with no pigmented scars adjacent to the areas of retinal necrosis. Toxoplasmosis in immunocompromised patients is not self-limiting as it is in imunocompetent patients.

53. Toxoplasma Retinochoroiditis Immunocompetent Immunocompromised

54. Toxoplasma Retinochoroiditis For active retinochoroiditis within 2-3 mm of the disc or fovea, which threatens vision, or peripheral lesion associated with severe vitritis , start first-line therapy for 3-6 weeks, as follows: (1) pyrimethamine 75 mg PO load,25 mg PO twice daily, plus, (2) folinic acid 3-5 mg PO twice weekly (to reduce the adverse effect of bone marrow toxicity of pyrimethamine ), and (3) sulfadiazine 2 g PO load, then 1 g PO 4 times daily.

55. D) Neuro -ophthalmologic manifestations 10-15% of patients who are infected with HIV common causes of neuro -ophthalmologic manifestations include Meningitis, Meningeal and Parenchymal Lymphoma, Neurosyphilis , and Toxoplasmosis.

56. Neuro -ophthalmologic manifestations include Papilledema due to increased intracranial pressure. Optic neuritis, Cranial nerve palsies, Ocular motility disorders, and Visual field defects

57. Treatment Radiation and Chemotherapy for Lymphoma Specific antibiotics for Infectious causes Systemic steroids are indicated in severe cases of optic neuritis (high dose, short course).

58. E) Orbital Manifestations The most common complications include Orbital lymphoma, Orbital cellulitis due to Aspergillus infection and Orbital Kaposi's sarcoma Lymphomas are treated with radiation and chemotherapy, whereas orbital cellulitis is amenable to systemic antibiotics.

59. F) OCULAR MANIFESTATION OF HIV INFECTION IN CHILDREN Fewer ocular manifestations of HIV infection and an especially low incidence of CMV retinitis. The reason for this difference is unknown, but may relate to an altered immune response to HIV or a lower prevalence of CMV seropositivity in children. HIV-infected children are, however, at increased risk for neurodevelopmental delay, a condition often associated with neuro -ophthalmic complications.

60. A fetal AIDS-associated embryopathy , with downward obliquity of the eyes, prominent palpebral fissures, hypertelorism , and blue sclerae , has also been described

61. G) Ocular Toxicity of Antiretroviral Drugs R ifabutin - intraocular inflammation uveitis- 33% Cidofovir - uveitis and intraocular hypotony - 25- 30% Didanosine - retinal pigment epithelial abnormalities; mottling and hypertrophy accompanied by overall decreased retinal function . Gancyclovir & Acyclovir - corneal epithelial inclusion termed corneal lipidosis. Lastly, long-term Atovaquone can corneal subepithelial deposits . These adverse effects are dose related and resolve following discontinuation of the drug, with the exception of the abnormal retinal pigment epithelial changes.

62. Thank you