Eye on cytomegalovirus: Unveiling the ophthalmic impact of cytomegalovirus

Abstract

BACKGROUND

Cytomegalovirus (CMV) is a ubiquitous herpesvirus that can cause significant ocular morbidity, particularly in immunocompromised individuals.

AIM

To summarize the current understanding of the ophthalmic impact of CMV, with a focus on its epidemiology, clinical manifestations, diagnosis, and management, ocular symptoms of CMV floaters, blurred vision, and loss of peripheral vision, eventually progressing to retinal necrosis and detachment. CMV retinitis (CMVR) is a sight-threatening condition that can lead to retinal detachment, blindness, and even death.

METHODS

We discuss the pathophysiology of CMVR, including the role of immune suppression and viral reactivation. We also examine the clinical features of CMVR, including its characteristic retinal lesions and associated ocular complications. Diagnostic approaches are reviewed, including polymerase chain reaction and fundus photography.

RESULTS

We discuss treatment options, including antiviral medications, intravitreal injections, and surgical interventions. Finally, we highlight areas of ongoing research and future directions in managing CMV-related ocular disease.

CONCLUSION

CMV poses a significant threat to ocular health, particularly in immunocompromised populations such as those with human immunodeficiency virus/acquired immune deficiency syndrome.

Key Words: Cytomegalovirus; Cytomegalovirus retinitis; Immune suppression; Ophthalmic impact; Immunocompromised; Polymerase chain reaction; Ocular morbidity

Core Tip: Cytomegalovirus (CMV) retinitis is a severe eye infection that primarily impacts immunocompromised individuals, leading to symptoms like blurred vision, blind spots, floaters, and potential retinal detachment, which can result in blindness. Diagnosis involves an eye examination, blood tests to detect CMV antibodies or viral DNA, and imaging techniques such as fundus photography and optical coherence tomography. Treatment includes antiviral medications such as ganciclovir, valganciclovir, foscarnet, and cidofovir, as well as potential laser surgery to repair retinal detachment. Strengthening the immune system with antiretroviral therapy is crucial for managing the infection in people with human immunodeficiency virus/acquired immune deficiency syndrome.

INTRODUCTION

Cytomegalovirus (CMV) is a herpesvirus that induces persistent latency following initial infection. It primarily affects monocytes, macrophages, and dendritic cells, reactivating in immunosuppressed states to induce clinical illness. CMV has been associated with several symptoms, including neurological issues such brain tumors and chronic inflammatory disorders such as periodontitis[1-3].

CMV is present serologically in 80% of the human population[1]. In non-immunocompromised individuals, it presents with little or no morbidity. Kobayashi et al[1] have also suggested that 0.2%-2% of live births suffer mother-child CMV transmission. The 30%-40% of these children will go on to present with ocular morbidities and of this number, 20% will eventually suffer significant visual deficits linked to this disease[2].

CMV is a ubiquitous pathogen belonging to the Herpesviridae family, known for its ability to establish lifelong latency and periodic reactivation[1]. In the realm of ophthalmology, CMV is particularly notorious for causing CMV retinitis (CMVR), a severe retinal infection predominantly affecting individuals with compromised immune systems, such as those with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), organ transplant recipients, and patients undergoing immunosuppressive therapy[3]. CMVR is characterized by its insidious onset and rapid progression, leading to significant visual impairment or blindness if left untreated[4]. The infection manifests through symptoms such as floaters, blurred vision, and loss of peripheral vision, eventually progressing to retinal necrosis and detachment[5]. Despite advancements in antiretroviral therapy (ART), which have significantly reduced the incidence of CMV retinitis in developed countries, it remains a prevalent concern in regions with limited access to healthcare[6].

Risk factors for CMVR primarily include conditions that weaken the immune system. Individuals with HIV/AIDS, especially those with a CD4 count less than 50, are at high risk. Other significant risk factors include organ transplantation and the use of immunosuppressive drugs, such as those used in cancer therapy or after organ transplants[7]. Additionally, local ocular immunosuppression, such as steroid injections in the eye, can also increase the risk[8,9]. Even without systemic immunosuppression, these factors can predispose individuals to CMVR[8,9].

This paper aims to provide a comprehensive overview of CMV in Ophthalmology, focusing on its pathophysiology, clinical manifestations, diagnostic methods, and current treatment strategies with particular reference to CMVR. By elucidating the complexities of CMVR, we hope to underscore the importance of early detection and intervention in mitigating the disease’s impact on vision and quality of life.

MATERIALS AND METHODS

Studies on CMV in eye care were sought using the PubMed search engine. The keywords “cytomegalovirus” “cmv” “retinitis” “eye care” were used to generate the following search string; ["cytomegalovirus" (MeSH Terms) OR "cytomegalovirus" (All Fields)] OR ["cytomegalovirus" (All Fields) AND "cmv" (All Fields)] OR "cytomegalovirus cmv" (All Fields) AND ["retinaldehyde" (MeSH Terms) OR "retinaldehyde" (All Fields) OR "retinal" (All Fields) OR "retina" (MeSH Terms) OR "retina" (All Fields) OR "retinally" (All Fields) OR "retinals" (All Fields) OR "retinitis" (MeSH Terms) OR "retinitis" (All Fields)] AND ["eye" (MeSH Terms) OR "eye" (All Fields)] AND "care" (All Fields).

RESULTS

A total of 97 records were returned, ranging from 1988 to 2024. Records not available for free online were excluded, returning 28 items. The Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA)[10] diagram (Figure 1) below shows the selection criteria. The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist. The aims of the studies used in this review are listed in Table 1 below.

Figure 1  The Preferred Items for Systematic Reviews and Meta-Analysis diagram that shows the selection criteria.

Table 1 Types of studies used in the review.

Category	Number of studies	Key findings
Diagnosis	10	Gold standard with polymerase chain reaction; fundus photography imaging, etc.
Treatment	12	Efficacy of valganciclovir; other antiviral agents
Management	6	Treatment and follow-up in immunosuppressed individuals

DISCUSSION

Overview of results

This systematic review underscores progress in CMV diagnostics, treatment, and management, specifically focusing on the efficacy of polymerase chain reaction (PCR) for early detection and valganciclovir for treatment. Fourteen studies were review articles, 7 of them were case reports, and a further 7 were longitudinal studies.

Potential biological mechanisms

CMV reactivation encompasses complex pathways, such as the inhibition of T-cell responses, enhancement of pro-inflammatory cytokines, and disruption of host cellular processes.

The immune system is a highly organized complex arrangement of intersecting biomolecular systems that primarily maintains the normal functionality of all cells and tissues of the organism in which it exists[11]. The immune system is dependent and interconnected with other human tissues and systems. Consequently, an optimally functioning immunity is required for the clearance of apoptotic cells (efferocytosis), tissue repair and healing, maintaining homeostasis, and preventing sustained inflammatory response[12]. CMV has been known to interfere with the functionality and control of the host immune system through the direct suppression of certain immune cells[13], alteration in cytokine proliferation[14], and the downregulation of major histocompatibility complex (MHC) expressed on the surface of viral laden cells[15-18]. However, these immunocompromising cascades are contained in a host with an optimally functioning immunity. Thus, the expression of the CMV gene and its subsequent clinical manifestation after the latency period is predominantly seen in immunocompromised and immuno-immature individuals[7]. The various clinical manifestations associated with CMV infection are due to the hijacking of certain biomolecular signaling pathways by the reactivated CMV secondary to the inadequate or incorrect immune response to the proliferating viral genes[19]. Furthermore, factors such as stress, chronic inflammatory response, pregnancy, immune-modulating drugs, nutritional deficiency, aging, and co-morbidities such as diabetes and HIV/AIDS can modify the biochemical cascades that initiate the cell-mediated immunity and alter the biomolecular processes required for the modulation of anti-inflammatory cytokines consequently, resulting in the complex cascades that result in the reactivation of CMV[20-23]. The factors mentioned earlier, and the immune-modulating actions of CMV eventually trigger the various biomolecular pathways required to initiate the reactivation of latent CMV. These pathways include altered production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumour necrosis factor-alpha[24], suppression of T-cell response by immune-modulating diseases and drugs, and altered regulatory T-cell action[24,25]. The induction of transcription factors such as activator protein-1 and nuclear factor kappa-light-chain-enhancer of activated B-cells (nuclear factor kappa B) is caused by by reactive oxygen species[26-28], DNA (deoxyribonucleic acid) hypomethylation and the destructive effects of heat shock proteins[29,30]. The ophthalmic manifestations of CMV may range from mild ocular disorders to serious ocular diseases that can result in profound vision loss[31]. The mechanisms have been summarized in Table 2 for clarity[13-18,20-30].

Table 2 The mechanisms of cytomegalovirus reactivation.

Mechanism	Description	Ref.
Direct suppression of immune cells	CMV interferes with the functionality and control of the host immune system through the direct suppression of certain immune cells	Fornara et al[13]
Alteration in cytokine proliferation	CMV alters the proliferation of cytokines, impacting the immune response	Compton et al[14]
Downregulation of MHC	CMV downregulates MHC expressed on the surface of viral-laden cells, impairing immune recognition	Vancíková and Dvorák[15], Gabor et al[16], Park et al[17], Howard and Najarian[18]
Altered production of proinflammatory cytokines	Reactivation involves the altered production of proinflammatory cytokines such as IL-1, IL-6, and tumour necrosis factor-alpha	Chinta et al[24]
Suppression of T-cell response	Immune-modulating diseases and drugs suppress T-cell response, contributing to reactivation	Chinta et al[24], Döcke et al[25]
Altered Treg action	Changes in Treg action affect immune regulation and promote reactivation	Chinta et al[24], Döcke et al[25]
Induction of transcription factors	Reactive oxygen species induce transcription factors like activator protein-1 and nuclear factor kappa B, leading to gene expression changes associated with CMV reactivation	Janeway et al[26], Heald-Sargent et al[27], Dhar et al[28]
DNA hypomethylation	Hypomethylation of DNA impacts gene expression and can contribute to the reactivation of CMV	Pshenichkin et al[29]
Effects of HSP	Destructive effects of HSPs facilitate reactivation	Boom et al[30]
Stress and chronic inflammatory response	Stress and chronic inflammation alter biochemical cascades, leading to reactivation	Iwatani et al[20], Mariotti et al[21], Cook et al[22], Hanaoka et al[23]
Pregnancy	Pregnancy-induced changes in the immune system can trigger reactivation	Iwatani et al[20], Mariotti et al[21], Cook et al[22], Hanaoka et al[23]
Immune-modulating drugs	Drugs that modulate the immune system can contribute to reactivation	Iwatani et al[20], Mariotti et al[21], Cook et al[22], Hanaoka et al[23]
Nutritional deficiency	Lack of essential nutrients impacts immune function and may lead to reactivation	Iwatani et al[20], Mariotti et al[21], Cook et al[22], Hanaoka et al[23]
Aging	Age-related decline in immune function increases the risk of reactivation	Iwatani et al[20], Mariotti et al[21], Cook et al[22], Hanaoka et al[23]
Co-morbidities (e.g., diabetes, HIV/AIDS)	Co-existing health conditions like diabetes and HIV/AIDS alter immune responses and facilitate reactivation	Iwatani et al[20], Mariotti et al[21], Cook et al[22], Hanaoka et al[23]

AIDS: Acquired immune deficiency syndrome; CMW: Cytomegalovirus; HIV: Human immunodeficiency virus; HSP: Heat shock proteins; IL: Interleukin; MHC: Major histocompatibility complex; Treg: Regulatory T-cell.

Clinical implications

These findings emphasize the necessity for prompt and precise diagnosis to reduce disease progression and vision impairment, especially in resource-constrained environments. Diagnosis of CMV in general and ophthalmic settings can range from simple ocular examinations using an ophthalmoscope to more sophisticated techniques like PCR assays.

Investigation of CMV

Diagnoses of CMV can be ophthalmic examination based or laboratory based. While ophthalmic imagery and examinations offer rapid diagnoses, they are most effective in the symptomatic stages of the disease. Laboratory diagnoses take longer to complete, but can potentially pick out the disease in early stages before signs and symptoms appear.

Ophthalmic diagnoses; fundus photography: Fundus photography is a non-invasive imaging technique used to capture detailed retinal images, aiding in the diagnosis of CMVR)[31-35]. Advances in digital color fundus imaging have largely replaced traditional film and slide transparencies due to their convenience and efficiency while still providing comparable accuracy for classifying and measuring CMVR[36]. This method is considered a potential alternative to indirect ophthalmoscopy for detecting CMVR in resource-limited settings, although further research is needed to assess its diagnostic accuracy and feasibility[37]. While typically managed by trained eye care professionals[38], non-experts can also achieve high accuracy in diagnosing CMVR among people living with HIV, though variability suggests that extensive training is necessary for reliable remote screening[39].

Fundus photography effectively identifies and monitors CMVR, allowing for timely diagnosis and treatment, and has shown strong agreement with indirect ophthalmoscopy in HIV-positive individuals[40]. It also holds promise for integration into machine learning protocols for CMVR detection[41]. Additionally, fundus photography can detect CMVR in non-HIV patients undergoing specific treatments[42] and identify unilateral chorioretinal macular scars in children with congenital CMV infection[43].

The technique is valuable for documenting optic disc neovascularization and vitreous hemorrhage in people living with HIV and CMVR[44], and can assess other abnormalities, such as microvascular retinopathy, in AIDS patients with low CD4⁺ counts who have not yet received highly active ART (HAART)[45]. It reveals a high incidence of ocular pathology in patients co-infected with AIDS and syphilis, including HIV-related microvascular retinopathy, CMVR, vitreous inflammatory opacity, and syphilis-related retinopathy[46,47]. Color fundus photography has also been used to capture optic nerve aplasia associated with congenital CMV infection[48].

Serial color fundus photography, particularly when combined with spectral domain optical coherence tomography, is essential for evaluating CMVR and identifying specific patterns of chorioretinal involvement[49-51]. Advanced automated mosaic software such as i2k Retina or AutoMontage enhances the quality of composite images for diagnosing and monitoring CMVR compared to other programs like IMAGEnet[52]. The ultra-wide-field Optomap imaging system, capturing a larger portion of the retina and peripheral CMVR lesions, has been preferred by patients for its comfort and shorter imaging time[53]. Wide-field fundus photography also reveals that recurrent CMVR after hematopoietic stem cell transplantation is characterized by increased marginal activity in previously stable lesions and new yellow-white lesions around atrophic and necrotic areas[54].

Despite its strengths, fundus photography shows a strong correlation with clinician assessments of retinitis area but often estimates these areas as smaller. Both fundus photography and clinical assessments have a negative correlation with visual field outcomes[55]. Different reading centers achieve good, though not perfect, agreement on CMVR presence and extent, with moderate consistency in grading disease progression[56]. However, limited sensitivity in detecting small and peripheral lesions indicates a need for improved imaging techniques for better accuracy[1].

Laboratory diagnoses

PCR: PCR is a critical diagnostic method for detecting CMVR and other ocular infections, offering precise disease classification with low misclassification rates when combined with characteristic clinical features[57]. The laboratory technique surpasses traditional culture methods in detecting CMV and other ocular pathogens, making it invaluable for diagnosing a broad range of ocular infections[58]. This method is highly reliable, demonstrating excellent sensitivity and specificity in diagnosing uveitis and endophthalmitis by detecting CMV and other infectious pathogens in ocular fluids[59].

In cases of viral anterior uveitis where the symptoms may overlap[60], PCR plays an important role to specifically identify the causative viruses of which CMV is one of them[61-65]. Additionally, PCR effectively identifies CMV as a common pathogen in co-infected cases of infectious panuveitis, with CMV-positive eyes showing better visual outcomes compared to CMV-negative eyes[66]. This precise detection characteristic of PCR is essential for guiding targeted antiviral and anti-inflammatory treatments to prevent serious visual impairment complications such as secondary glaucoma[67]. For example, PCR is particularly important in regions like southern Taiwan, where CMV is a prevalent cause of anterior uveitis often linked with glaucoma and pseudophakic eyes[68]. However, in the United States, cases of anterior uveitis that underwent anterior chamber paracentesis with PCR did not show a significant proportion of CMV-positive results[69].

Similarly, PCR analysis is vital for diagnosing and managing viral uveitic conditions, efficiently identifying infections caused by human herpesviruses (HHV) such as herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus, CMV, and Toxoplasma gondii[70], particularly in immunosuppressed patients[71-75]. Its utility extends to detecting less common viral causes, such as HHV-7, identified as the cause of herpetic anterior uveitis in a rare case[76]. Additionally, PCR identifies CMV as a co-infecting pathogen in multifocal serpiginoid choroiditis, guiding the use of specific antiviral therapies like valganciclovir[77]. While PCR can detect viral DNA, such as CMV, in pterygium tissue, its presence may not always be significant enough to prove a causal role in the disease[78]. In cases of hypertensive anterior uveitis, PCR positivity significantly influences treatment decisions and prognosis, especially when distinctive keratic precipitates are present[79]. A study conducted in Thailand identified CMV as the most prevalent cause in such cases[80].

Furthermore, PCR plays a vital role in diagnosing CMV in cases of corneal endotheliitis of unknown cause, allowing for targeted treatment and effective monitoring, particularly in patients experiencing corneal edema or post-keratoplasty graft edema[81]. In South Korea, for instance, multiplex PCR was successfully used to accurately identify CMV among other HHV in patients with corneal endotheliitis accompanied by high intraocular pressure, underscoring the technique's importance in managing viral corneal endotheliitis[82]. Additionally, PCR has proven crucial in detecting CMV in a case where it prevented the misdiagnosis of bilateral dendritic epithelial keratitis, initially suspected to be caused by HSV in an immunocompromised patient[83]. This highlights CMV’s ability to affect the cornea without involving the retina[84].

Real-time PCR (RT-PCR) analysis of aqueous humor is an important diagnostic tool for identifying CMV and other infectious causes in about one-third of uveitis cases, improving the accuracy of etiological classification[85,86]. However, PCR testing of aqueous humor, including for CMV, does not significantly aid in diagnosing Fuchs’ uveitis, which relies primarily on clinical evaluation[87]. On the other hand, PCR is crucial for diagnosing CMV anterior uveitis accurately, with machine learning techniques demonstrating a very low misclassification rate[57]. This method is highly sensitive and specific for detecting CMVR in AIDS patients[88]. Additionally, it has identified a significant association between ocular Torque Teno virus and CMVR in uveitis patients with systemic immunodeficiency[89].

Quantitative RT-PCR, a specific type of quantitative PCR (qPCR), is particularly effective in confirming CMV in viral retinitis. It reveals a significant correlation between viral DNA copy number and the extent of clinical involvement, especially when samples are collected early in the disease[90]. Additionally, qPCR is useful for monitoring CMV DNA levels in anterior segment infections, showing that ganciclovir therapy helps in viral clearance, while glucocorticoid treatment might impede this process in immunocompetent individuals[91]. In contrast, digital droplet PCR offers greater sensitivity and accuracy than qPCR for detecting CMV in aqueous humor, facilitating early diagnosis and effective treatment monitoring in pathogen-induced Posner-Schlossman syndrome[92].

Moreover, PCR analysis of vitreous samples is essential in vitrectomy cases for detecting CMV and other infectious agents, aiding in the differentiation between infectious, inflammatory, and malignant conditions[93]. When combined with cytokine profiling, PCR becomes highly effective for diagnosing intraocular lymphoma, providing near-perfect sensitivity and specificity for identifying immunoglobulin heavy chain gene rearrangements[94]. Furthermore, it is crucial in cases involving retinal vascular inflammation, optic nerve involvement, extensive retinitis, or in immunocompromised patients, where it helps guide appropriate treatment[95]. Identifying the viral cause of a severe intraocular inflammatory syndrome like acute retinal necrosis is also essential, as PCR analysis findings allow for the rapid initiation of targeted therapy[96-98].

In cases of congenital CMV infection, PCR confirmation using saliva or urine samples is commonly used for screening newborn babies[99,100]. It also suggests that CMV may not be a major cause of congenital cataracts, indicating the need to reassess the role of serology in diagnosing viral etiologies in these cases[101].

Management

Acute retina necrosis, the most common condition caused by the herpesvirus family, could also be caused by CMV and the VZV. The standard of treatment typically involves the use of combination therapy, which includes intravitreal and systemic antiviral medications, as well as topical and systemic steroids; in some cases, there is a need for surgical intervention. Although not properly studied, the use of laser barricade has been suggested as adjunctive therapy in the management of acute retina necrosis[102]. Tasiopoulou et al[103] reported a series of patients with systemic lymphoma who developed CMV, and subsequently responded very well to the use of oral and intravitreal antiviral medications such as valganciclovir and intravitreal foscarnet injection. In a retrospective study, Markan et al[104] showed that oral valganciclovir was a better alternative for treating CMVR than intravitreal ganciclovir. The affordability of valganciclovir would help to reduce the burden associated with CMVR. Asberg et al[105] proved oral valganciclovir to be non-inferior to intravenous injection of ganciclovir in patients undergoing solid organ transplantation.

Gupta et al[106] described favorable outcomes in patients with CMVR when carrying out adoptive immunotherapy using CMV-specific Cytotoxic T-lymphocytes. Patients with AIDS-related CMV have been reported to be prone to developing CMVR after the initiation of treatment with combined ART; an ophthalmologist must examine the eyes so that prompt diagnosis can be reached and immediate treatment with specific anti-CMV therapy in addition to combined ART[107]. Chiu et al[108] reported myelosuppression after the use of ganciclovir in the management of CMVR; the combination of intravenous ganciclovir and CMV immunoglobulin therapy led to better visual outcomes and reduced CMV viral load. Apart from the retina or choroidal complications sequelae to CMV infection, keratitis has also been identified as a rare potential complication[109]. This necessitates the consideration of CMV as a potential cause of keratitis when a patient presents with keratitis, anterior uveitis, and ocular hypertension, which should be treated with antiviral medications such as systemic ganciclovir rather than steroidal medications, intraocular pressure-reducing or cycloplegic agents alone. The ISIS Antisense Oligonucleotides have been shown to have antiviral and pharmacokinetic properties that are beneficial in treating retinitis secondary to CMV[110]. Belatacept, an anti-nephrotoxic, non-diabetogenic agent used to improve graft survival in patients who underwent transplants, has been found to lead to an increased incidence of CMVR[111]; hence, there could be a need to discontinue such medication and explore other options such as calcineurin inhibitors etc. Advances in biotechnology led to the development of fomivirsen, an antisense RNA molecule used to treat CMVR[112]. Drugs targeting the UL54 and the UL97 DNA polymerase have been restricted to some extent due to their nephrotoxicity[113].

Antivirals

The increase in the prevalence of CMVR can be linked to an increase in HIV, this necessitates the use of HAART in patients presenting with CMV[112]. Valnoctamide a neuroactive mood stabilizer that inhibits the growth of CMV in brains still in development has been found to have anti-CMV potential[114].

Frequent monitoring of PCR in a patient who underwent hematopoietic stem cell transplantation was and has been the gold standard in the prevention of CMV for a long time. Antiviral chemoprophylactic drugs such as letermovir are beneficial as a pre-emptive measure (prophylaxis), especially in patients undergoing allogeneic transplantation[115,116]. Intravitreal antiviral drug implants have also been used in the management of ocular complications of CMV[117]. Intravitreal ganciclovir implants should be replaced when old ones are exhausted[118,119]. Keratitis is one of the potential complications of CMV, depending on the extent of cornea involvement, treatment may range from the need for surgery on the cornea to the use of antiviral agents such as intravitreal ganciclovir. The incidence of cornea endothelitis is relatively common in middle-aged men, cornea endothelitis could present with signs similar to Posner Schlossman syndrome necessitating prompt diagnosis and immediate initiation of treatment[120].

Intravitreal steroids

Steroids have been found to have deleterious effects on CMV, hence it is advisable to abstain from their use post-confirmation of CMV. Suárez-Lledó et al[121] found that it had a negligible effect on patients with low risk of CMV but increased the incidence of CMV in patients at high risk.

Surgical interventions

Due to the ocular potentially damaging sequelae of CMV, such as retinal detachment, choroidal neovascularization, cystoid macula edema, etc, surgical intervention such as photocoagulation and injection of anti-vascular endothelial growth factors might be needed to prevent further degeneration of the eye. There may also be a need for pars plana vitrectomy in cases of vitreous hemorrhage, silicone oil tamponade or photolaser coagulation in cases of retinal detachment[122]. The selection of a surgical approach in the management of retinal detachment secondary to CMVR is dependent on the mechanical factors of the detachment and the expected survival rate of the patient or immune system[123,124]. The need for glaucoma surgery due to cornea endothelitis and anterior uveitis could arise due to CMV[125].

Research and future directions in CMV management

CMVR remains a significant challenge in the field of ophthalmology, particularly among immunocompromised patients, such as those with HIV/AIDS or undergoing organ transplantation. Current management primarily relies on antiviral medications, with ganciclovir and foscarnet being the cornerstones of treatment. Despite their efficacy, these drugs have limitations, including potential toxicity and the risk of viral resistance. Ongoing research is focused on improving these therapies and developing new ones[126]. One promising direction is the use of novel antiviral agents that target different stages of the CMV life cycle or enhance the body's immune response to better control the infection[127]. For example, newer compounds such as letermovir are being investigated for their ability to suppress CMV replication more effectively while minimizing side effects[116].

In addition to drug development, there is an increasing emphasis on the role of personalized medicine in managing CMVR[124]. Advances in genomics and proteomics offer the potential to tailor treatments based on individual patient profiles, including genetic predispositions and specific viral strains[128]. Research into biomarkers is also underway to better predict disease progression and treatment responses[129]. Such personalized approaches could lead to more effective and less toxic treatment regimens, thereby improving patient outcomes and quality of life. Furthermore, the integration of molecular diagnostics in routine clinical practice is expected to enhance early detection and monitoring of CMVR, allowing for timely and targeted interventions[130].

Looking to the future, innovative therapeutic strategies, such as gene therapy and immunomodulation, are on the horizon[131]. Gene therapy offers a way to correct the underlying genetic factors contributing to CMV infection or enhance the body's ability to fight the virus. Immunomodulatory approaches, including the use of immune checkpoint inhibitors or cytokine therapies, aim to boost the immune system's capacity to control CMV more effectively[131]. These cutting-edge treatments are still in experimental stages but hold promise for revolutionizing the management of CMVR. As research progresses, the hope is that these new strategies will lead to more durable and less invasive treatments, ultimately transforming the landscape of care for patients affected by this challenging condition.

Limitation

The authors could not access a number of records because they were not available for free.

CONCLUSION

In conclusion, CMV poses a significant threat to ocular health, particularly in immunocompromised populations such as those with HIV/AIDS. CMVR remains a leading cause of vision loss in these individuals, emphasizing the need for early diagnosis and prompt treatment. Advances in antiviral therapies, coupled with enhanced diagnostic techniques, have improved patient outcomes; however, challenges persist in managing the infection and preventing recurrence. Continued research is essential to develop more effective treatments and to understand the mechanisms of CMV pathogenesis in the eye. Strengthening immune function through ART remains a cornerstone in the comprehensive management of CMVR, underscoring the interplay between virology and immunology in eye care. Through ongoing advancements and a multidisciplinary approach, we can aspire to mitigate the impact of CMV on vision and improve the quality of life for affected individuals.