Disease Overview:
Almost all of us have a virus named cytomegalovirus (CMV) in our bodies. Generally, the body's defense system prevents the virus from causing any complications. Yet, if for any reason, our body's mechanisms for defense against infections are critically weakened, the cytomegalovirus can cause severe diseases. This is typically noticed in individuals with AIDS. In these individuals, the most usual way for the disease to cause harm is by attacking the light-sensitive part of the eye (retina). Bleeding and Inflammation caused by the disease will eventually harm the retina and may result in blindness. This is known as CMV retinitis.
The positive news is that if any patient receives the appropriate combination of treatments, the chance of getting this disease is reduced. Now, medical therapy is available. There are many ways of delivering drugs to treat cytomegalovirus retinitis, which are summarized below:
Daily injections administered via an intravenous infusion
A tiny implant in the back portion of the eye that delivers medicine through a timed-release mechanism
Oral medicines are taken several times daily
Monthly injections are given into the white part of the eye
The route of administration simply depends on the medicinal product. The patient will need to discuss CMV treatment choices with his/her health specialist.
Symptoms of Cytomegalovirus (CMV) Retinitis:
Cytomegalovirus retinitis symptoms can start with a slow onset of floaters with blurred vision over a few days. This can be responsible for a loss of peripheral (side) vision. Sometimes the symptoms start with a blind spot in the core of vision and can cause a loss of central vision. The symptoms typically happen first in the first eye but then progress to the second eye. In absence of treatment or improvement in the immune system, the disease destroys the retina and damages the optic nerve. This causes decreased vision or even blindness. Individuals with this disease will often develop a detached retina.
Treatment of Cytomegalovirus (CMV) Retinitis:
Cytomegalovirus retinitis (CMV) should be treated quickly due to its rapid progression. If not managed, it will progress towards the posterior pole at a standard rate of 24 mm daily, and the zone of retinitis grows at a rate of 750 microns every 3 weeks. Growing necrotizing retinitis can cause the destruction of the whole retina in 3 to 6 months if ignored. Highly active antiretroviral therapy has been significant and crucial in the role of immune reconstitution in those with HIV/AIDS suffering from Cytomegalovirus retinitis. Its use helps improve CD4+ cell counts, reduce HIV replication, and reduce mortality in all those with AIDS. Thereby, immunocompromised individuals with CMV retinitis should first begin HAART prior to beginning other treatments. There are different modes of therapy including systemic, intravitreal, and combined systemic and intravitreal treatment. The objective of treatment is to stop acute inflammation and slow down the time to relapse.
Systemic Therapy:
Systemic antivirals are the gold standard of treatment for Cytomegalovirus retinitis. First-line treatment for both HIV +Ve and HIV -Ve individuals with CMV retinitis is typically induction therapy with either IV ganciclovir or oral valganciclovir, followed by maintenance therapy. Due to the poor bioavailability of oral ganciclovir, it is not the preferred treatment as induction therapy but reserved for primary prophylaxis and maintenance therapy.
Induction therapy is typically given at a dose of 5 mg/kg every 12 hours for 2 to 3 weeks days, and can also be used as maintenance therapy at a dose of 5 mg/kg daily. Limiting factors of long-term therapy with intravenous ganciclovir include adverse reactions such as myelosuppression, catheter-related sepsis, as well as the development of resistance.
Valganciclovir is a kind of oral prodrug that is quickly converted to ganciclovir in the body. The medicine has been shown to be as promising as intravenous ganciclovir, and because of its good bioavailability, it can be considered both an induction therapy and maintenance therapy.
Foscarnet is typically used as a second-line therapy for Cytomegalovirus (CMV) retinitis, specifically for Cytomegalovirus retinitis that is resistant to medicines ganciclovir or valganciclovir, or for those who can not be treated with ganciclovir because of dose-limiting neutropenia or leukopenia. Induction therapy generally consists of Foscarnet 180 mg/kg total daily and Foscarnet 90 mg/kg daily for maintenance, ranging from weeks to months, administered intravenously. It has been demonstrated that in patients with CMV retinitis and HIV/AIDS, the medicine foscarnet offers a survival benefit over treatment with intravenous ganciclovir.
Cidofovir is one more antiviral drug administered intravenously that has activity against Cytomegalovirus retinitis. Because of adverse effects, such as nephrotoxicity, neutropenia, ocular inflammation, and ocular hypotony, probenecid is given prior to and after infusion of cidofovir, as well as IV fluids, to scale down renal toxicity
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The use of systemic therapy with foscarnet sodium, ganciclovir, and cidofovir, is related to resistance. A medicine named Letermovir, which targets CMV viral terminase complex (UL56), is currently only FDA approved as a prophylactic agent for Cytomegalovirus (CMV) retinitis but has been studied as a potential antiviral therapy in those with resistance to other existing therapies.
Intravitreal Therapy:
Foscarnet and Ganciclovir can be given via intravitreal injection and have been used for CMV retinitis. The appropriateness for intravitreal therapy is that administration of these medicines to the areas of the infectious procedure can block viral concentrations in the vitreous while avoiding complications that may accompany systemic therapy. As per studies, the weekly injections of intravitreal ganciclovir are promising in treating the original infectious stage of the illness. Although, the use of any of these drugs as sole therapy is uncommon; it is often used along with systemic treatment.
Combination Therapy:
In cases of resistant Cytomegalovirus retinitis, a combination of medicine foscarnet 24mg/mL in 250 mL and intravenous ganciclovir, or oral valganciclovir and intravenous foscarnet, has been found to be more promising than monotherapy. Those who have had previous treatment for Cytomegalovirus retinitis, have relapsed and can tolerate the medicines, can try a combination of foscarnet 24mg/mL injection and ganciclovir, or any combination of systemic therapy and intraocular therapy in order to control/manage their Cytomegalovirus retinitis.
Conclusion:
Cytomegalovirus retinitis is a vision-threatening opportunistic infection that may still affect patients living with HIV/AIDS in the post-highly active antiretroviral therapy era. Following anti-CMV and HIV therapy, immune recovery may be responsible for adverse complications such as immune recovery uveitis, and treatment with anti-CMV medicines may be responsible for adverse reactions that require laboratory and health monitoring.
Cytomegalovirus (CMV) retinitis in the post-highly active antiretroviral therapy era carries an improved prognosis, and incidence has notably declined. However, because these patients still have high mortality rates in comparison to the rest of the population, all those having a weakened immune system should be properly screened, with guidance dependent on the CD4+ counts.
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