A Review Study on Ocular Posterior Segments & Neuro-Ophthalmic Manifestations Associated with Human Immunodeficiency Virus (HIV) Infection and its Management Options

: To describe the various types of ocular posterior segment and neuro-ophthalmic manifestation associated with Human Immuno-deficiency virus (HIV) infection. And also describe the management or preventive measures associated with it. In all cases of ocular disease due to HIV, there is only one reason i.e. immune system. A Descriptive study was done to review the articles available on PubMed, Google Scholar, Medline, Publon, Orcid, Healthstar, Science Open, Cochrane Library, Paperity and others related to the ocular complications associated with HIV infections. Peer-reviewed articles/ studies were referred to ascertain the available screening tests, preventive measures, hygiene, neuro-ophthalmic manifestation and management options for HIV patients. Some authors suggest that ocular posterior segment & neuro-ophthalmic manifestation due to HIV infection is not recovered, but few authors suggest that it can be recovered with the help of highly active antiretroviral therapy (HAART) in combination with some preventive measures and hygiene. The Eye-care professional’s responsibility is to spread awareness about the complications related to the eye and their management or preventive measures. Ocular complications are very diverse and relatively frequent in the case of HIV infection. Commonly it is associated with a concurrent diagnosis of depression, anxiety, panic, attack and psychiatric disorders, etc. There are various management or preventive measures like regular eye examinations, follow-up of the HIV patients, following the preventive measures strategies, taking therapy properly, preventing to spread of the infection, etc. retinitis, chorioretinitis,


Ocular toxoplasmosis (OT)
Ocular toxoplasmosis in people with HIV is typically of the acquired variety, and reactivation occurs more frequently than not. [31][32] According to an Indian study, 2.8 percent of patients had ocular toxoplasmosis, the second most frequent ocular infection. [17] HIV-positive people who have atypical toxoplasmosis may experience localised, multifocal, or diffuse necrotizing retinitis with illdefined borders and haemorrhages or without them. Additionally, they might exhibit active retinochoroiditis close to a retinochoroidal scar. It is more likely that a toxoplasmic infection caused the nearby retinal vasculitis (Kyrieleis' arteriolitis) and varied degrees of vitreal inflammation (mild to extensive) in the presence of low CD4+ T cell numbers. Toxoplasmic chorioretinitis has the potential to become fulminant and can mimic CMVR as well as other ocular OIs including syphilis. In most cases, early diagnosis and treatment gives satisfactory results. The most commonly used treatment plan combines clindamycin with/without pyrimethamine and sulfadiazine. Another medication is azithromycin. Oral corticosteroids, which should only be taken in conjunction with antiprotozoal medications, can reduce inflammation, but their usage should be cautious due to the clear systemic hazards of further lowering host immunity, which exceed their advantages. [33] In addition to systemic therapy, intravitreal clindamycin is beneficial and shows promise, particularly in aggressive OT. [34][35][36]

Ocular Tuberculosis
In India, Asia, and Latin America, tuberculosis (TB) is still endemic. According to studies from India, [37] OTB, which manifests as choroidal trabeculae, sub retinal abscess, conjunctival tuberculosis, and panophthalmitis, was observed in 3.8% of HIV patients in the pre-HAART era. [38] Ocular TB could be a sign of a miliary disease or be considered a component of a widespread systemic illness. Typically, they are discovered during a regular ocular examination as asymptomatic choroidal tubercles. The ocular course does not usually match the course of the systemic disease, and they can happen in all CD4 count levels. [17], [37] Along with HAART, systemic antitubercular therapy (ATT) is the preferred course of treatment. [39][40] MDR TB is potentially 10 times more common in HIV positive patients than HIV negative people. [41] Patients with HIV infection require more sophisticated management of MDR TB. [42][43][44]

Ocular syphilis
It has experienced a revival, particularly in cases of HIV co-infection among people at high risk for it, such as sex workers and men who have sex with males (MSM). [45][46] It is known as "the great imitator" since it can imitate any uveitic organism. Anterior

Retinal toxicity and optic neuropathy
Didanosine, which has been discontinued from HAART regimens in the majority of nations, has been linked to reports of retinal toxicity [54]. There have also been reports of maculopathy linked to ritonavir and efavirenz. [55][56] Ethambutol, linezolid, and the relatively new medication combination of elvitegravir/cobicistat have all been linked to reports of optic neuropathy. [57] 2. Choroiditis 2.1 Pneumocystis P. carinii can cause conjunctivitis, orbital masses, optic neuropathy, and choroiditis in the eyes. [58] It is typically observed as bilateral and multifocal, well-defined yellow choroidal lesions in the posterior pole that are not connected to vitritis, iritis, or vasculitis. [59] Induction and subsequent maintenance therapy with systemic pentamidine, trimethoprim and sulfamethoxazole, or dapsone are effective in treating ocular lesions in the majority of cases.

Cryptococcus
The most frequent cause of AIDS-related neuro-ophthalmolgic lesions is cryptococcus meningitis. In addition to being linked with eyelid nodules, conjunctival masses, granulomatous iritis, iris masses, vitritis, necrotizing retinitis, endophthalmitis, and optic neuritis, cryptococcal choroiditis can also be multifocal, solitary, or confluent. [60] Even in the era of HAART, 200 mg/day of fluconazole maintenance medication is currently advised for all patients.

Meningitis
HIV-associated meningitis can develop as a result of viral infections, but it can also manifest as papilledema, neuritis, or direct involvement of the optic nerve with neuropathy or increased intracranial pressure. [61][62][63][64][65] Cryptococcus and tuberculosis were shown to be the causes of infectious meningitis in sub-Saharan Africa in 19-68% and 1-36% of cases, respectively. [66] Initial diagnoses of bacterial meningitis were made in 1.6 percent of cases, but subsequent molecular and microbiological analyses indicated tuberculosis in 2.5 percent of cases, neurosyphilis in 2.6 percent, toxoplasma in less than 1 percent, and viral aetiology in a small number of other cases. In people with HIV, Cryptococcus is the most frequent cause of meningitis, and it can cause optic neuropathy either directly or indirectly. [65], [67][68][69] Up to 75% of patients with cryptococcal meningitis have intracranial hypertension, which can subsequently result in optic disc oedema. Due to the fact that both the infection and the intracranial pressure need to be treated, the initial course of treatment frequently entails antifungal therapy coupled with pressure-lowering techniques utilising transient lumbar drains or shunts. Common ophthalmic symptoms were nystagmus or impaired smooth pursuit in 26% and 22% of patients, respectively, as well as optic disc edoema in almost 30% of cases and cranial nerve palsy in 17% of patients. Both pain during eye movement and acute vision loss only occasionally happened. [70][71]

Retinal Microangiopathy and Neuroretinal Disorder
For individuals with a differential diagnosis of visual loss due to optic nerve or retinal involvement, neuro-ophthalmic examination is often advised. Patients at risk for infectious diseases that damage the retina and choroid include those that are less prevalent, such as cryptococcosis, tuberculosis, pneumocystis, and syphilis, as well as cytomegalovirus (CMV), herpesvirus, and toxoplasmosis. [72] These infectious choroiditis/retinitis patients frequently have spectacular physical findings and are evaluated by retinal and uveitis experts rather than being referred for neuro-ophthalmic research. HIV infection, however, also causes microvascular abnormalities that damage the retina, optic disc, and cornea, as well as a neuroretinal condition where the layer of retinal nerve fibres is thinned. [73][74][75][76][77][78] Indirect HIV infection of the neuroretinal tissue, chronic immunological activation, microvascular ischemia, accelerated ageing brought on by HIV infection, and chronic immune activation are all possible secondary causes of neuroretinal disease. [79][80] The neuroretinal condition is more likely to develop in HIV individuals who have more severe or advanced disease. Lower CD4 + T cell numbers also have some association. These patients' eyesight loss will be minimal to moderate, and their contrast sensitivity will be diminished. [81] The multifocal electroretinogram (mERG) and the pattern electroretinogram (pERG) both show abnormalities. [82]

Eye Movement Abnormality
With HIV, abnormal eye movements are known to happen. [83][84][85] The most frequent abnormalities found to happen even in persons without additional clinical signs of HIV infection are abnormal smooth pursuits and saccades. [86] HIV infection has also been linked to cranial nerve palsies, though the prevalence varies depending on the community. [83] The sixth and third cranial nerves have the highest frequency of palsies. The third nerve and sixth nerve were damaged alone or in combination, and the patients frequently reported headache, diplopia, and impaired vision. [87] 6. Pupil Involvement Lesions infiltrating the brainstem may be the source of pupillary abnormalities in HIV infection. Anisocoria and light near dissociation are examples of these. Researchers have also discovered that patients with HIV had irregular pupil cycle times, which may indicate subclinical ocular autonomic dysfunction. [88] Anywhere along the sympathetic chain may have lesions, which can cause Horner's syndrome. The Argyll Robertson pupil, a classic example of neurosyphilis, is characterised by uneven, small-sized pupils and light-near dissociation. Despite the fact that dorsal midbrain syndrome can present with light-near dissociation, this observation is extremely specific for syphilis.

HIV PREVENTION
Since proper use of condoms should entirely prevent HIV transmission as well as transmission of many other sexually transmitted infections, condom use has been a cornerstone of HIV prevention in men. However, the efficiency of condoms has been estimated to be about 80% against heterosexual HIV transmission and 70% against male-to-male sexual transmission [18][19]. These lower than anticipated effectiveness estimates are likely caused by over-reporting of condom use; however incorrect use and condom failure also have an impact. [20] While syringe exchange programmes have not completely stopped HIV transmission in drug users, supplying clean injection equipment can significantly lower HIV transmission in injectable drug users [21]. To supplement these fundamental preventative techniques, more tools are required. 1. Prevention of mother-to-child transmission.

MANAGEMENT/TREATMENT OF OCULAR COMPLICATIONS
The management of ocular AIDS complications is challenging. Since the majority of ocular opportunistic infections cannot be completely eliminated, lifelong suppressive medication is required for their care. Patients who have had their endogenous immunity restored as a result of HARRT are an exception. [22] Depending on the patient's immunological status and the site of the active retinitis, CMV retinitis is treated on an individual basis. The FDA has authorized 7 medications to treat CMV retinitis. Oral and injectable treatments for the system include ganciclovir sodium, foscarnet sodium, and cidofovir (ganciclovir and valganciclovir). [22][23] Systemic Therapy -Highly Active Anti-Retroviral Therapy (HAART) In India, NACO offers free HAART to everyone living with HIV. HAART guarantees that those who are ill will live longer and have higher quality of life. [33] With HAART, HIV patients can now live a life that is more similar to that of people with chronic conditions like diabetes or high blood pressure.

CONCLUSION
Ocular manifestations associated with HIV infection range greatly in kind and are very common. One of the essential treatments for HIV-positive people is routine follow up for ocular examination. Its main goal is to stop the progression of visual loss. Additionally, it permits indirect monitoring of the effectiveness of therapy, any relevant development of resistance, and patient compliance as well as long-term compensation of the immunological status of HIV-positive patients. Ocular problems may be the first clinical sign of HIV infection in some people, indicating HIV positivity. The prevalence of sightthreatening CMV retinitis, which, despite aggressive treatment, remains the most common cause of blindness in HIV positive people, has significantly decreased as a result of the prevention of opportunistic infections and the development of highly efficient ART.