Varicella Zoster Virus-Induced Retinitis and Retinal Detachment in an Immunocompetent Patient: A Case Report

Introduction

Acute retinal necrosis (ARN) and progressive outer retinal necrosis are forms of necrotizing herpetic retinopathies that constitute ophthalmological emergencies, although with low incidence rates [1,2]. Herpes simplex type 2 is the most common etiological agent of necrotizing herpetic retinopathies, followed by cytomegalovirus and Epstein-Barr virus [3]. Necrotizing herpetic retinopathies associated with varicella zoster virus (VZV) occurs sporadically and typically presents with ARN features [1]. The disease affects immunocompetent hosts and initially manifests as unilateral anterior uveitis accompanied by pain [3].

In contrast, progressive outer retinal necrosis occurs almost exclusively in immunocompromised individuals [4] and is characterized by rapid progression of necrotizing lesions in the posterior pole and macula [1,3]. Both ARN and progressive outer retinal necrosis can lead to severe complications, including retinal detachment, optic nerve atrophy, and blindness [5]. Early diagnosis and prompt administration of specific antiviral therapy are crucial [6].

The diagnosis of ARN is based on clinical criteria established by the American Uveitis Society in 1994. These criteria include characteristic foci of retinal necrosis, rapid disease progression, circumferential spread, occlusive vasculopathy, vitritis, and anterior chamber inflammation.

First-line treatment for VZV retinitis consists of immediate systemic (oral or intravenous) antiviral agents combined with adjuvant intravitreal injections. Additional therapeutic measures include topical and oral corticosteroids, anticoagulants, prophylactic retinal laser photocoagulation, and vitrectomy [7]. Despite optimal management, the prognosis remains guarded for patients with severe immune dysfunction [6]. The condition’s low prevalence often complicates early accurate diagnosis and appropriate intervention.

Case Report

A 56-year-old man was referred to the hospital with a 7-day history of substantial painless vision acuity (VA) deterioration in the left eye. The patient’s history revealed that, 4 weeks prior, he had an upper respiratory tract infection and presented with fluid-filled blisters on the forehead above his left eye. He had received a diagnosis of VZV infection, which was based on skin examination and medical history. He had experienced excessive yellowish discharge from the left conjunctival sac. He did not consult either the family doctor or an ophthalmologist. He denied any chronic diseases and was otherwise healthy. At the age of 27 years, he underwent scleral buckling of a left eye for retinal detachment.

Clinical examination at admission revealed that the best corrected visual acuity (BCVA) measured by the Snellen chart was 0.8 in the right eye and 0.4 in the left eye. The patient presented a positive relative afferent pupillary defect in the affected left eye and no pain in eye movement. The pneumatic tonometry showed values of 14 mmHg in the right eye and 12 mmHg in the left eye. Examination of the right eye was unremarkable. A further slit-lamp examination of the left eye showed significant blepharoconjunctivitis, light sensitivity, a branching dendritic corneal lesion indicating dendritic keratitis (fluorescein stained), and keratic precipitates of the cornea. The anterior chamber of the left eye was filled with pathological hazy fluid. Dilated fundus photography of the left eye manifested vitritis, grade-4 optic disc edema, and exudative retinal detachment, including macula (Figure 1). Further clinical examinations revealed signs of vasculopathy with hemorrhages and multifocal retinitis at the posterior pole. Retinal detachment was present in the upper and temporal quadrants (Figure 2). Ultrasonography of the left eye confirmed the previous findings.

A fluorescence angiogram of the left eye revealed areas of blocked fluorescence in the perimacular region in an early-phase examination. Furthermore, the photograph revealed late-phase plentiful leakage from the optic disc and slight leakage from the inferior arcade’s retinal vessels (Figures 3–5). Optical coherence tomography picture of the macula of the left eye was unsuccessful, due to the abundance of exudative retinal detachment. The right eye fundus examination, fluorescein angiogram, and optical coherence tomography of the macula were non-revealing. Computed tomography scans of the head were unremarkable. Results of the HIV, T spot, syphilis immunoglobulin (Ig) G, rubella IgG, Lyme disease IgG, and hepatitis C virus tests were negative. The patient was seronegative for Legionella, Epstein-Barr virus toxoplasma gondii, and cytomegalovirus. The other blood tests, such as complete blood count, comprehensive metabolic panel, and electrolytes, did not show any significant abnormalities.

Due to the high suspicion of ARN, based on clinical examination and advanced clinical presentation, the patient was empirically started on antiviral treatment and received intravenous acyclovir 1 g 3 times daily, with frequent topical corticosteroids.

After 4 days of antiviral use, the patient declared better vision and a lack of pain. BCVA was 1.0 in the right eye and 0.5 in the left eye. Pneumatic tonometry showed values of 14 mmHg and 12 mmHg in the right and left eye, respectively. Slit-lamp examination of the anterior chamber and fundus of the left eye did not present with significant improvement. The right eye examination was unremarkable.

From the fifth day, the patient reported vision deterioration in the left eye. After the fifth day of pharmacotherapy, the VA was light perception inferiorly and from a temporal site. Tonus measured in the left eye showed a value of 12 mmHg. The sub-retinal fluid did not disappear with the treatment, and massive exudative retinal detachment remained intact. After the medical consultation, the date of pars plana vitrectomy (PPV) was set on the day after the eighth dose of pharmacotherapy. PPV of the left eye consisted of retinectomy, laser photo-coagulation with endolaser, and high-viscosity (5700 cs.) silicone oil tamponade. Aqueous humor and vitreous humor tap did not result in active virus replication, due to the previous effective pharmacotherapy. The procedure was uncomplicated. The day after, the patient’s BCVA was 0.25. Tonus measured pneumatically was 10 mmHg. A slit lamp clinical examination of the left eye revealed the presence of subconjunctival hemorrhage and optically clear, cell-free anterior chamber fluid. A fundus examination showed residual disc edema, macula without reflex, and retina reattached in the examined fundus and periphery. The patient was discharged on the day after the surgery on 16 mg of oral prednisolone added to the therapeutic regimen and 1g of oral acyclovir 3 times daily for 12 weeks.

During the first follow-up visit (1 week after the PPV) the patient’s BCVA was 0.25. Pneumatic tonometry measured an intraocular pressure of 14 mmHg. A dilated fundus examination revealed residual disc edema and macular edema. The clinical examination did not show abnormalities other than on the day of discharge from the hospital. The patient was furthermore coming every week for measurement of the intraocular pressure, which was always within normal limits.

During the second follow-up visit (1 month after the PPV) the patient’s BCVA was 0.16. The pneumatic tonometry result was 13 mmHg. The dilated fundus examination did not differ from that of the previous visit. The retina was attached to the examined area. No pathologies were detected. The patient status remained constant with the improvement in the VA.

During the third follow-up visit (3 months after the PPV), the patient’s BCVA was 0.16. The pneumatic tonometry measured an intraocular pressure of 16 mmHg. A dilated fundus examination indicated an attached retina in each quadrant in the coincidence of emulsified silicone oil. Given the compromised tamponade effect, the patient was scheduled for the planned silicone oil removal. The patient’s VA was equal to that of the previous visit. The pharmacological treatment was modified during the follow-up visits. The prednisolone dose was gradually decreased over time, and acyclovir was discontinued after a planned 12-week therapy.

The patient was admitted after 4 months of the PPV procedure for the silicone oil removal, due to the oil emulsification and fulfillment of the attachment role in the eye. Three-port PPV was chosen as a technique for silicone oil removal, to ensure an adequate perspective in the retinal completion. The procedure was performed without complications, and no sub-retinal fluid accumulation was visualized. Several fluid-air and air-fluid exchanges were used to remove the residual emulsified bubbles. The retinal attachment was ensured at the end of the surgery. The ports were closed without suture, because of the use of 27-gauge equipment during the surgery.

The day after the procedure, the clinical examination revealed a BCVA of 0.32. Intraocular pressure measured pneumatically was 11 mmHg. The fundus examination showed an attached retina at the examined area.

Discussion

The case report demonstrates the rapid progression of zoster infection in the ocular region. Within approximately 1 week of VZV reactivation, the patient developed advanced ARN and proliferative vitreoretinopathy with exudative retinal detachment in the perimacular area of the left eye. Although anti-viral therapy was administered, the initial panuveitis persisted. The presence of vitritis and exudative retinal detachment with retinal necrosis necessitated PPV [7,8]. ARN typically presents with severe complications, including vision loss. Clinical examination of a dilated eye in patients with ARN can reveal panuveitis [9]. Common findings include vitritis, retinal necrosis, occlusive vasculature in the posterior pole and optic disc, and macular edema [10]. The underlying etiology significantly influences prognosis, with VZV ARN patients facing a higher risk of retinal detachment than those with herpes simplex virus infection [11]. Diagnosing ARN presents challenges due to its variable manifestations, ranging from mild to severe. A comprehensive review of potential causes is essential, beginning with mandatory immunocompetence laboratory testing [6]. The differential diagnosis should consider progressive outer retinal necrosis, cytomegalovirus, syphilis, Candida albicans endophthalmitis, acute multifocal hemorrhagic retinal vasculitis, sarcoidosis, atypical peripheral toxoplasmic retinochoroiditis, and Behçet syndrome [12]. Factors such as socioeconomic status, age, and medical history significantly influence diagnostic confirmation [13]. According to the British Ophthalmological Surveillance Unit, ARN incidence rates range from 0.5 to 0.63 cases per million annually [14]. Advances in PCR techniques and flow cytometry have enhanced pathogen identification accuracy, enabling targeted therapy and improving outcomes. Identification of pathogens allows for direct therapy against the disease [7]. First-line treatment typically combines systemic and intravitreal antivirals to reduce disease severity and prevent advanced complications. This targeted approach decreases the risk of vision loss and retinal detachment incidence in the affected eye [15,16]. In our patient’s case, systemic steroids were initiated after antiviral therapy, followed by PPV. Steroids, being potent anti-inflammatory agents, were administered postoperatively to suppress cytokine response and reduce retinal structure edema [17]. PPV has proven effective in eliminating inflammatory mediators and completely removing proliferative vitreoretinopathy in the atrophic retina [18]. However, due to their multifocal effects, these interventions are reserved for severe courses of ARN cases with vitritis and significant optic disc or macula involvement [19]. To prevent fellow eye infection, oral acyclovir should follow intravenous administration [7]. Multiple studies examining the adjunctive use of intravitreal foscarnet or ganciclovir have yielded encouraging results in reducing the incidence of severe vision loss and retinal detachment [20]. Adjunctive intravitreal therapy probably decreases the risk of vision loss; however, it was not practiced in the case of our patient. According to Baltinas et al, approximately two-thirds of eyes affected by ARN progressed to retinal detachment, regardless of whether patients received oral, intravenous, or combined intravitreal antiviral therapy [21]. Based on the results of the previous studies, demonstrating that despite the combination of forms of antiviral treatment methods, the final VA was poor, we decided not to administer the injections.

Viral inflammatory particles serve as risk factors for humoral and cell-mediated proinflammatory mechanisms. Their contribution to vasculopathies, including occlusive complications in patients with ARN, warrants antiplatelet therapy with aspirin (500–650 mg daily) [22].

Despite significant advances in ophthalmic treatment, ARN remains one of the most challenging ophthalmological conditions. The prognosis depends on multiple factors, and preserving vision in the affected eye proves exceptionally difficult [15,22].

Future research should focus on developing treatments to improve BCVA. The literature indicates that extensive retinal inflammation correlates with increased retinal detachment risk and poorer BCVA prognosis [15]. Currently, there is no standardized classification system for retinal changes in ARN, nor are there established treatment algorithms. The disease’s unpredictable course, influenced by various factors, precludes a one-size-fits-all treatment approach. While systemic acyclovir may accelerate acute retinal lesion regression and potentially reduce second eye involvement, it does not prevent retinal detachment [23]. In our patient’s case, the progression of cumulative subretinal fluid and exudative retinal detachment caused severe visual impairment, necessitating PPV to reduce overall inflammation and proliferative vitreoretinopathy, allowing macular and optic disc areas to heal. Retinal detachment represents the most serious complication of any ocular disease. In ARN cases, even immediate administration of acyclovir and steroid therapy cannot prevent retinal detachment occurrence. The risk of retinal detachment in patients with ARN is estimated at 75% to 85%, with initial symptoms typically appearing within 3 months of onset [6,24]. Prior literature indicates the highest rate of retinal detachment onset within 3 to 6 months following initial ARN diagnosis [24]. In the present case, retinal detachment was present upon hospital admission.

Peripheral laser photocoagulation has been established as an effective prophylactic procedure for retinal detachment [23]. An alternative approach involves early PPV combined with endophotocoagulation [25]. Debate continues regarding the optimal treatment strategy. Early PPV for ARN likely represents the most effective method for eliminating inflammatory mediators and proliferative vitreoretinopathy in the necrotic posterior pole [18]. In our patient, pronounced exudative retinal detachment required PPV with endolaser photocoagulation of the peripheral retina as well as retinectomy at the necrotic regions. While the literature lacks consensus on the criterion standard for retinal detachment treatment in ARN patients, some studies demonstrate successful outcomes with PPV supplemented by intravitreal acyclovir administration for secondary retinal detachment prevention [8,25,26]. ARN complicated by retinal detachment, proliferative vitreoretinopathy, and panuveitis diminishes the likelihood of full recovery with justifiable BCVA [9]. Despite advanced ophthalmological care and technological progress of diagnostic and therapeutic tools, patients with ARN face relatively poor BCVA outcomes. Complications such as traction or rhegmatogenous retinal detachment and optic nerve involvement pose particular risks [24], given that ARN can lead to other threatening conditions, including ocular hypotony, macular edema, proliferative vitreoretinopathy, epiretinal membrane, optic atrophy, and phthisis. Considering those complications, we recommend that VZV vaccination be promoted, especially among elderly and immunocompromised populations [26]. The patient’s BCVA at the 3-month follow-up visit was 0.25. The clinical examination did not show abnormalities, other than at the discharge. As the literature suggests, younger patients experience better VA gain after treatment [25].

Silicone oil serves as a crucial tamponade agent following vitreoretinal procedures. It must be extracted from the eye within 3 to 6 months after surgery. Failing to remove it in time can trigger complications, including glaucoma, cataract formation, hyperoleon, and keratopathy [27].

To minimize the risk of retinal redetachment after oil removal, surgeons should perform a 360-degree encircling buckle and endolaser treatment during the initial operation [28]. The preferred technique for silicone oil removal is a 3-port pars PPV, as it enables clear visualization of retinal status [29]. Any detected retinal breaks or subretinal fluid must be addressed immediately during the removal procedure [21,27]. Multiple exchanges between fluid-air and air-fluid, as they were made in the case of our patient, help eliminate remaining emulsified oil droplets that might otherwise become trapped in the ciliary sulcus or pars plana region [30]. A sutureless surgical approach for silicone oil removal reduces tissue trauma and accelerates healing. When the retina remains attached despite oil emulsification, it suggests a lower risk of retinal detachment.

Our research showed that when ARN is caused by VZV and leads to retinal detachment, patients who undergo PPV tend to have worse VA results. However, according to the above-cited literature, younger patients showed better improvement in their VA. While our study demonstrated the efficacy of single therapy with systemic antiviral agents, several critical aspects of treatment remain unexplored. These include the optimal treatment duration, need for long-term prophylactic therapy, and role of corticosteroid therapy in visual outcomes. Further research is necessary to address these questions.

The primary limitation of this study was its retrospective design and inclusion of only 1 case. Moreover, the surgical interventions performed during PPV were not compared with other possibilities. Another limiting factor was the lack of experience with the treatment of ARN. Among the other limitations, we include the lack of properly organized differential diagnosis and very early start of medications, without previous vitreous and aqueous humor tap to confirm the pathogenic factor.

Conclusions

This case report highlights the challenges in the diagnosis and treatment of VZV retinitis etiology in emergency settings. Due to the low epidemiology of ARN, the treatment schedule has no characteristic universal pattern and the treatment must be patient-oriented. Given the progressive nature of complications, VZV retinitis should be considered in any patient presenting with retinal necrosis ARN features, regardless of immune status. Prompt systemic antiviral therapy combined with steroids is crucial for preserving eye function. In our patient’s case, despite initial clinical improvement, the patient’s vision deteriorated to light perception only. At admission, the patients’ BCVA was 0.4 in the left eye. After 5 days of continuous antiviral therapy, the subretinal fluid persisted, and massive exudative retinal detachment remained unresolved. Over time, previously satisfactory clinical outcomes turned to vision deterioration, necessitating PPV. On the day of PPV, the patient’s VA was qualified as perception of light. The procedure was performed without complications. A silicone oil tamponade was used due to the size of retinal detachment. At 1 day and at 1 week after PPV, the patient’s BCVA was 0.25. Furthermore, 1 month and 3 months after the PPV, the patient’s BCVA was up to 0.16. A dilated fundus examination did not differ from the previous visit. The retina was attached in the examined area. Based on the postoperative examination 1 day after the silicone oil removal procedure (which was performed 4 months after the initial PPV), the patient’s BCVA was 0.32. Intraocular pressure measured pneumatically was 11 mmHg. The fundus examination showed an attached retina at the examined area.

PPV resulted in significant improvement, even in the presence of severe panuveitis and necrotizing retinitis. We recommend the active promotion of VZV vaccination to help prevent serious reinfection complications, particularly in elderly and immunocompromised individuals.