Clinical features of cytomegalovirus retinitis, A retrospective analysis of 90 patients

doi:10.21203/rs.3.rs-4715667/v1

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Clinical features of cytomegalovirus retinitis, A retrospective analysis of 90 patients

https://doi.org/10.21203/rs.3.rs-4715667/v1

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Background

To analyze the clinical features of patients with cytomegalovirus retinitis and provide evidence for a better understanding of the disease.

Methods

A retrospective analysis was conducted on the clinical manifestations of 90 patients with cytomegalovirus retinitis. The analysis included general data, visual acuity, intraocular pressure, anterior segment examination, vitreous body examination, and color fundus photography.

Results

The patients' ages ranged from 1 to 64 years, with 59 males and 31 females. Among the 90 patients, 18 had acquired immune deficiency syndrome (AIDS) as a secondary condition, 70 had various types of hematological diseases following bone marrow transplantation, 1 had a history of thymus extraction, and 1 had congenital autoimmune hemolytic anemia. Of the affected eyes, 35 cases were monocular and 55 were binocular. Anterior chamber inflammation was observed in 67 eyes out of 145 affected eyes, while 40 eyes showed significant vitreous inflammation. Some cases exhibited typical "cheese and ketchup" changes during fundus examination, with various fundus manifestations observed. Based on the extent and location of the lesions, they were classified into diffuse, hemilateral, and focal types.

Conclusion

Cytomegalovirus retinitis is more prevalent among immunodeficient individuals rather than those with normal immune systems. Regular eye examinations are recommended for patients of AIDS diagnosis and bone marrow transplantation. Understanding the clinical characteristics of the disease can aid in early diagnosis and treatment.

Health sciences/Diseases

Health sciences/Risk factors

cytomegalovirus retinitis

acquired immune deficiency syndrome

allogeneic hematopoietic stem-cell transplantation

Cytomegalovirus (CMV) is a double-stranded DNA virus belonging to the beta genus of the Herpesviridae family, with a protein shell and a lipoprotein envelope. CMV commonly infects healthy individuals, but most cases result in either latent infections or mild symptoms[1]. Data indicates that CMV infection rates range from 30–70% in developed countries and from 90–100% in developing countries.[1–2]

The clinical manifestations of CMV infection are complex, and the consequences can be severe in immunodeficient patients. The most common CMV infections manifest as interstitial pneumonia, enteritis, and esophagitis, which are well-recognized and can be identified early [3–6]. However, for less common infection sites, clinical understanding and experience are lacking. In particular, the early symptoms of ocular CMV infection are often mild and challenging to detect.

Cytomegalovirus retinitis (CMVR) is characterized by chronic progressive necrotizing retinitis. Without treatment or timely intervention, the disease progresses rapidly and can lead to severe visual impairment[7–9]. This study summarized and analyzed the characteristics of 90 patients with CMVR to enhance understanding of the disease's atypical clinical manifestations. Timely treatment of CMVR can stabilize vision, prevent disease progression, and improve patients' quality of life.

General Data

A retrospective analysis was conducted on 90 patients with cytomegalovirus retinitis from March 2016 to April 2023 at Eye Hospital, China Academy of Chinese Medical Sciences, comprising 59 males and 31 females. The age of the patients ranged from 1 to 64 years, with the duration of the disease varying from 3 days to 4 years. This research protocols received ethical approval from the Eye Hospital, China Academy of Chinese Medical Sciences Ethics Committee. The committee decided to waive the need for written informed consent from the participants studied in this analysis as the data were analyzed retrospectively and anonymously.

Inclusion Criteria

The diagnostic criteria for including standard CMVR were as follows:①Fundus examination revealing white sheathing of retinal veins, retinal hemorrhage, irregular patchy retinal edema, and necrosis.②Positive testing of CMV nucleic acid in the intraocular fluid.

Examination Items

Clinical symptoms, visual acuity, intraocular pressure, Anterior chamber inflammation, and anterior vitreous body observed through slit-lamp microscopy, retina observed via mydriatic and indirect ophthalmoscopy, fundus photography, fundus fluorescence angiography (in some patients), and other patient information were collected for statistical analysis.

General Data

Among the 90 patients with CMV retinitis, 59 were male, representing 65.6% (59/90) of the total. There were 31 female patients, accounting for 34.4% (31/90). The age of the patients ranged from 1 to 64 years, and the duration of the disease varied from 3 days to 4 years. There were 35 cases of monocular disease (38.9%) and 55 cases of binocular disease (61.1%). Additionally, there were 18 cases secondary to acquired immune deficiency syndrome (AIDS), making up 20% (18/90) of the total. Furthermore, 70 cases were secondary to bone marrow transplantation, representing 77.8% (70/90). As our hospital's Hematology Department is a national key department, we have a large number of patients, especially post-bone marrow transplant. There was 1 case following thymus extraction, accounting for 1.1% (1/90), and 1 case of autoimmune hemolytic anemia, also representing 1.1% (1/90).

Eye condition

Complaints and Intraocular Pressure

Among the 90 patients, there were 8 cases of sudden vision loss, 48 cases of blurred vision, 21 cases of dark shadows floating or occluding the eyes, and 7 cases of dark spots before the eyes. Additionally, there were 6 cases without any discomfort. The intraocular pressure (IOP) of 145 eyes in these 90 patients was measured using a non-contact tonometer, with values ranging from a minimum of 6 mmHg to a maximum of 45 mmHg. For patients with an IOP greater than 21 mmHg, the IOP was monitored at each follow-up visit, and it could be controlled within the normal range by using IOP-lowering drops and locally controlling inflammation.

Anterior chamber Condition

Among the 145 eyes of the 90 patients, 67 eyes exhibited keratic precipitates (KP). Of these, 43 eyes mainly showed granulomatous KP (Fig. 1A), while 22 eyes displayed nongranulomatous KP (Fig. 1B), and 2 eyes had pigmented KP. The remaining 78 eyes did not show KP. KP was often accompanied by plankton in the anterior chamber. Posterior iris adhesions were observed in only 3 out of the 145 eyes of the 90 patients, with 2 eyes belonging to AIDS patients and 1 eye to a bone marrow transplant patient.

Vitreous Condition

In 40 out of 145 eyes of the 90 patients, vitreous inflammatory cells were visible, accounting for 27.6% (40/145). Vitreous hemorrhage was observed in 3 eyes, while no obvious abnormalities were found in the vitreous body of the remaining 102 eyes.

Fundus Condition

The fundus manifestations mainly included typical necrotizing retinitis, with the white sheath of retinal veins commonly visible (Fig. 2A). Yellow and white retinal lesions along the retinal vasculature, with granular active edges, often accompanied by retinal hemorrhage, were also observed (Fig. 2B). The presence of vascular sheath, exudation, and retinal hemorrhage simultaneously resulted in a fundus appearance resembling cheese and tomato paste. The retinal blood vessels exhibited frosty dendritic changes. Additionally, white or yellowish-white patchy or clustered exudative lesions of the medial retina were noted, which may fuse with or without retinal hemorrhage. Old CMVR could be identified by observing retinal fiber scarring and subretinal crystal formation (Fig. 2C). Among the 145 eyes of the 90 patients with CMVR, retinal detachment occurred in 9 eyes. Optic disc were involved in 76 out of the 145 eyes, with 56 eyes showing papilloedema with an unclear boundary and 20 eyes displaying disc hemorrhage.

According to the scope and location of the lesions involved in relevant literature[10–11], CMVR could be divided into diffuse, hemilateral, and focal types. In 90 cases with 145 eyes, 64 eyes were classified as diffuse type(Fig. 3A). The fundus exhibited involvement of the entire retina, with lesions extending to blood vessels in all four quadrants of the posterior pole and the optic disc. The hemilateral type accounted for 33 eyes (Fig. 3B): The lesions involved half of the retina with clear boundaries. The focal type accounted for 48 eyes (Fig. 3C): Retinal lesions were confined to only one quadrant. Fundus fluorescence angiography revealed that retinal veins, along with the white sheath of blood vessels, exhibited fluorescent staining of the vessel walls, with nearby areas showing punctate hyperfluorescence. In contrast, areas corresponding to retinal hemorrhage and granular necrosis displayed low fluorescence, which decreased as the angiography time extended (Fig. 2D).

Visual acuity

Visual acuity ranged from non-light perception (NLP) to 0.3 in 70 eyes. Most of these patients exhibited involvement in the posterior pole of the retina, with the majority of fundus changes being diffuse. There were 24 eyes with visual acuity greater than 0.3 and less than or equal to 0.5, and most of them showed local retinal involvement. In 38 eyes, visual acuity exceeding 0.5 involved the peripheral retina. The best visual acuity recorded was 1.0 in 8 eyes, and the macular region was not involved. All 13 eyes that did not pass the vision test belonged to infants. In terms of visual acuity, those involving the macula, leading to macular hemorrhage and edema, generally had poor visual acuity, while those affecting the peripheral retina had good visual acuity.

Cytomegalovirus belongs to the human species-specific herpesvirus type 5, falling under the ß subfamily and possessing a double-stranded DNA structure. People are generally susceptible to cytomegalovirus, but most of them are recessive carriers or exhibit no obvious symptoms[1–3]. CMV is widely prevalent in China, with the positive rate of anti-CMV IgG in adult serum exceeding 90% in clinical tests, often without clinical symptoms. Following CMV infection, the virus often remains in the early stage of the replication cycle, leading to latent infection. Cytomegalovirus primarily resides in human salivary glands, mammary glands, kidneys, and other organs, with the ability to hide in host epithelial cells, endothelial cells, peripheral mononuclear cells, and other cell types[12].

Currently, the number of AIDS patients in China is increasing, and cytomegalovirus retinitis is a common eye complication among AIDS patients, accounting for 1/4 to 1/3 of AIDS-related eye manifestations and being a primary cause of vision loss. Cytomegalovirus retinitis often serves as the initial symptom in most AIDS patients. Moreover, with advancements in technology, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become an effective treatment method for malignant blood diseases. Infections are the most common complications associated with allo-HSCT, with various infections observed throughout the transplantation process. Due to pretreatment, the use of immunosuppressants, and immune function deficiencies in patients undergoing hematopoietic stem cell transplantation, various infections may arise. Activated cytomegalovirus, which typically lies dormant in all organs, can lead to diseases affecting multiple organs[13–15].

According to the data from this study, among the 90 patients with CMV retinitis, 18 cases were secondary to AIDS, 70 cases were secondary to bone marrow transplantation, 1 case was secondary to thymus extraction, and 1 case was secondary to autoimmune hemolytic anemia. This finding aligns with previous reports indicating that CMV retinitis frequently occurs in immunosuppressed patients. The reason for the high incidence of CMVR after bone marrow transplantation in our hospital is that our hematology department is a national key discipline, with a majority of patients undergoing bone marrow transplantation, which leads to a high proportion of post-bone marrow transplantation patients among the 90 cases we have, resulting in the high incidence rate.

Cytomegalovirus infection is a major complication and a leading cause of death following allogeneic hematopoietic stem cell transplantation. Although reports on this disease are not uncommon both domestically and internationally, many doctors are still unfamiliar with it, leading to misdiagnosis. Therefore, it is necessary for us to enhance doctors' understanding of this disease. [16–17]. Our data revealed that 70 out of 90 patients developed secondary CMV retinitis after bone marrow transplantation, with clinical manifestations similar to those seen in AIDS-related CMV retinitis. This highlights the importance of vigilance for CMV retinitis in patients experiencing visual impairment or shadows before their eyes post-bone marrow transplantation, emphasizing the need for regular screening by experienced ophthalmologists to prevent delayed treatment.

In summary, CMVR exhibits the following characteristics:

①It predominantly affects individuals with compromised immune function, particularly AIDS patients and those who have undergone hematopoietic stem cell transplantation, potentially leading to blindness if not promptly treated[18–20].

②Clinical manifestations include bilateral or unilateral onset, with early symptoms possibly being mild, such as central and peripheral dark spots or no symptoms at all. Granulomatous KP or nongranulomatous KP may be observed. In some cases, the anterior chamber may not be involved, while others may present with vitreous floaters or even vitreous hemorrhage. Typical fundus changes can resemble cheese and tomato sauce, involving either the entire retina or a portion of it. The white sheathing of retinal blood vessels is common, resembling frost branches. Pigment scars of varying sizes begin to form after approximately 4 to 6 weeks, potentially leading to retinal detachment due to scarring[21–24].

In conclusion, immunocompromised patients should promptly seek evaluation at an ophthalmology department upon experiencing eye discomfort symptoms. Even asymptomatic individuals post-bone marrow transplantation or with AIDS should undergo regular eye examinations to facilitate early detection and treatment of the disease.

Ethics approval and consent to participate: This research protocols received ethical approval from the Eye Hospital, China Academy of Chinese Medical Sciences Ethics Committee. The committee decided to waive the need for written informed consent from the participants studied in this analysis as the data were analyzed retrospectively and anonymously.

Consent for publication: Not Applicable.

Availability of data and materials ：The datasets generated and/or analyzed during the current study are not all publicly available in order to protect patient anonymity, but are available from the corresponding author on reasonable request.

Competing interests: The authors declare that they have no competing interests.

Funding: This study was supported by High-level Traditional Chinese Medicine Hospital Projects at the Eye Hospital of China Academy of Chinese Medical Sciences. (GSP5-02).

Authors’ contributions: Y.Z and L.Y were the major contributor in writing the manuscript. G.Z designed the research. Y.Z, L.Y and N. L collected the patient data. All authors read and approved the final manuscript.

Acknowledgements: We thank Dr. Yong Tao for helpful discussions and technical assistance.

Author details: 1. Eye Hospital, China Academy of Chinese Medical Sciences, Beijing 100040, China;2. 2. Korla Hospital ,Xinjiang Production and Construction Corps Second Division, Xinjiang 841000 ,China;3. Yanqi Hospital ,Xinjiang Production and Construction Corps Second Division, Xinjiang 841100 ,China

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No competing interests reported.

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Clinical features of cytomegalovirus retinitis, A retrospective analysis of 90 patients

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