Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

Examining the etiological factors resulting in retinal detachment following prophylactic vitrectomy in the context of acute retinal necrosis syndrome.

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.

Use of intravitreal antiviral injection during vitrectomy in the treatment of acute retinal necrosis: anatomic and visual outcomes.

PURPOSE: To investigate whether intravitreal antiviral injection (IAI) during vitrectomy reduces the postsurgical retinal detachment (RD) rate and improves the visual prognosis of patients with acute retinal necrosis (ARN). METHODS: This retrospective cohort study included ARN patients treated at a tertiary hospital between January 2013 and December 2020. Patients who underwent pars plana vitrectomy (PPV) alone or combined with intraoperative IAI were classified in PPV-only group and PPV + IAI group, respectively. The incidence of postsurgical RD and the best corrected visual acuity (BCVA) between the groups was compared. A multivariate Cox hazard analysis was employed to explore the risk factors of postsurgical RD. A multivariate logistic regression analysis was applied to assess the impact of intraoperative IAI on preventing severe vision loss (SVL). RESULTS: Fifty-seven eyes with ARN with a median follow-up of 18.5 months were included in the study. There was no significant association between intraoperative IAI during vitrectomy and a reduced risk of postsurgical RD (hazard ratio [HR], 2.65; 95% CI, 0.71-9.89) or SVL at the 6-month follow-up visit (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.25-3.35). Better baseline best-corrected visual acuity (BCVA) was identified to associate with a higher risk of postsurgical RD (HR, 0.33; 95% CI, 0.14-0.81) and a lower risk of SVL at 6 months (OR, 2.28; 95% CI, 1.10-4.89). CONCLUSION: We did not observe a significant effect of intraoperative IAI on the anatomic and visual outcomes of ARN patients in this study. Intraoperative IAI may not be a necessary treatment option for ARN patients who receive vitrectomy.

Risk factors and prognostic factors associated with retinal detachment and visual outcomes in acute retinal necrosis.

OBJECTIVE: To investigate the risk factors and prognostic factors that affect the long-term clinical outcomes of acute retinal necrosis (ARN). METHODS: A retrospective study of patients with ARN who underwent treatment and completed follow-up in our ophthalmology department from 2011 to 2021 was conducted. The incidence and risk factors of retinal detachment (RD) and prognostic factors affecting long-term clinical outcomes, such as late-onset RD and final vision loss (< 20/200), were analyzed. RESULTS: Totally 59 ARN patients (65 eyes) with an average follow-up of 48.9 months were enrolled. During the follow-up period, RD occurred in 34 eyes (52.3%). The risk factors for RD included quadrants of involved retinal necrosis (odds ratio [OR], 4.181; 95% confidence interval [CI], 1.950-10.834) and initial intraocular viral load (OR, 1.721; 95% CI, 1.071-3.083). Early intravitreal antiviral treatment (OR, 1.204; 95% CI, 1.040-1.480) was independently associated with a decreased risk of late-onset RD. The factors independently associated with an increased risk of final vision loss were worse initial visual acuity (OR, 3.895; 95% CI, 1.551-13.662) and late-onset RD (OR, 8.043; 95% CI, 1.380-67.216). In addition, we utilized the fluctuating magnitude of viral load to quantify the extent of its reduction in comparison to its original value following the initial intravitreal antiviral injection (IAI). This ratio was strongly related to initial intraocular IL-8 concentration (Spearman correlation coefficient=-0.741, P = 0.000) and moderately related to the initial degree of aqueous flare (Spearman correlation coefficient=-0.508, P = 0.010). CONCLUSION: RD is a common and severe complication of ARN with multiple risk factors, such as initial retinitis involvement area and initial intraocular viral load. Active local antiviral therapy may reduce the risk of late-onset RD. The antiviral medication should be adjusted according to the inflammatory state. Therefore, timely detection of causative viruses and intensive systemic and local antiviral therapy is crucial for preserving visual function in ARN patients.

Acute retinal necrosis.

Acute retinal necrosis (ARN) is a rare, progressive viral uveitis, with the majority of cases caused by herpesviruses. The diagnosis of ARN is often delayed, and most patients will have some degree of permanent visual loss. We report a case of ARN in a previously healthy 32-year-old patient.

Acute retinal necrosis: clinical features, management and outcomes.

PURPOSE: To evaluate the clinical features, treatment, and visual outcome of patients with acute retinal necrosis (ARN). METHODS: The data of patients were retrospectively reviewed. Factors associated with visual loss and factors affecting the risk for retinal detachment (RD) development were evaluated. RESULTS: Twenty-four eyes of 24 patients (7 female/17 male, mean age 43.7 years, mean follow-up period 31.0 months) were included. In ocular fluid samples of 15 (83%) out of 18 eyes, polymerase chain reaction (PCR) tests were positive for herpes simplex virus (seven eyes; 39%), varicella zoster virus (six eyes; 33%), cytomegalovirus (one eye; 6%), and adenovirus (one eye; 6%). Central retinal occlusive vasculitis was observed in three (13%) eyes. Systemic antiviral therapy was given to all patients, and additional intravitreal ganciclovir was administered in seven eyes (29%). The most common complication was RD (46%). There was no statistically significant difference in the frequency of RD between herpes simplex virus- and varicella zoster virus-positive patients (p = .617). The rate of RD was similar in eyes undergoing prophylactic laser photocoagulation (LPC), eyes undergoing vitrectomy + LPC, and eyes not undergoing LPC (p = .237). The number of eyes with final visual acuity below 20/200 was significantly higher in eyes with RD than without RD (p = .047). CONCLUSION: Prophylactic LPC and vitrectomy did not show clear benefits in terms of preventing RD development. RD was the most common complication and a major factor for a poor visual prognosis.

Acute retinal necrosis in a patient on immunosuppressive treatment for COVID-19 pneumonia: a case report.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) occasionally develop ocular complications. We report a case of acute retinal necrosis (ARN) caused by Epstein-Barr Virus (EBV) that developed in a patient who had severe acute respiratory syndrome due to SARS-CoV-2 infection. CASE PRESENTATION: A 68-year-old woman complained of floaters and blurred vision in her right eye as she was receiving systemic prednisolone for COVID-19 pneumonia under isolation in our hospital. The patient visited an ophthalmologist following her discharge from the hospital and after the 2 weeks of isolation had ended. At the initial examination, her best-corrected visual acuity (BCVA) was 20/100 in the right eye, and the eye showed moderate anterior segment inflammation and vitreous opacities. Treatment was initiated with topical 0.1% betamethasone and 1.5% levofloxacin. After 1 month, the inflammation in the right eye decreased and her BCVA improved to 20/40. However, on day 48 from her initial visit, the inflammation in her right eye worsened and her BCVA decreased to 20/2000 by day 80. Pars plana vitrectomy with silicone oil tamponade was performed to remove the vitreous opacities, and expanded white exudates peripherally and retinal vessels with white sheathing suggestive of acute retinal necrosis (ARN) were seen intraoperatively. Analysis of the vitreous sample revealed EBV positivity on polymerase chain reaction. The patient was diagnosed with EBV-associated ARN and treated with systemic steroids and valaciclovir. The ocular inflammation gradually decreased, and she was discharged from the hospital. However, a week later, the inflammation in the right eye markedly worsened. Despite another course of steroids, the inflammation worsened, resulting in total retinal detachment and absolute glaucoma. Because of the severe pain, the right eye was enucleated. CONCLUSIONS: Clinicians should be aware that COVID-19 and immunosuppressive treatment can reactivate EBV in the eye.

Therapeutic prognostic factors associated with retinal detachment and visual outcomes in acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) is a fulminant necrotizing vaso-occlusive retinitis associated with a high incidence of vision loss. Prognostic factors associated with the treatment of ARN have not been comprehensively identified. This study aimed to determine therapeutic prognostic factors associated with long-term clinical outcomes in eyes with ARN. METHODS: This retrospective cohort study included patients with ARN who were treated between 2005 and 2019 in two tertiary ophthalmology departments in Seoul, Korea. Multiple logistic regression analysis was performed to investigate prognostic factors associated with late-onset retinal detachment (RD) and vision loss (<20/200). RESULTS: Sixty-one eyes with ARN with an average follow-up of 63.5 months were included. Surgical intervention of vitrectomy (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.004-0.47) and intraoperative prophylactic laser use (OR, 0.14; 95% CI, 0.02-0.81) were independently associated with a decreased risk of late RD. The factors independently associated with an increased risk of vision loss were worse initial visual acuity (OR, 3.28; 95% CI, 1.50-7.21), zone 1 involvement of necrotic retinitis (OR, 10.84; 95% CI, 1.62-72.41), and late-onset RD (OR, 5.38; 95% CI, 1.92-31.54). CONCLUSION: Vitrectomy and/or prophylactic intraoperative laser treatment may be effective treatment options in preventing delayed RD associated with an increased risk of vision loss in eyes with ARN.

Efficacy of prophylactic laser retinopexy in acute retinal necrosis: A systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis to assess the role of prophylactic laser retinopexy in preventing rhegmatogenous retinal detachment (RRD) in acute retinal necrosis (ARN). METHODS: Pubmed, Embase and Cochrane databases were searched for eligible studies from inception to July 2020. Comprehensive clinical demographics were extracted from each study by two independent investigators. A random effects model was selected to analyze the OR of RRD risk and visual outcome with 95%CI. Subsequent subgroup and sensitivity analysis were conducted to evaluate the source of heterogeneity. RESULTS: A total of eight studies and 247 eyes (111 prophylactic laser retinopexy eyes and 136 eyes receiving antiviral treatment) were included in this analysis. There was moderate statistical heterogeneity across all studies. When compared with routine antiviral treatment alone, RRD risk decreased in patients receiving prophylactic laser retinopexy, however, this was not statistically significant (P = 0.09, OR = 0.42, 95%CI: 0.15-1.15). There was significant improvement in BCVA during the follow-up period in the prophylactic laser retinopexy subgroup (P = 0.01, WMD = - 0.98, 95%CI: - 1.74, - 0.22). CONCLUSION: Based on current analysis, our results did not support convincing evidence of prophylactic laser in preventing RRD. Future studies featuring high-quality, multicenter trials will be required to correct baseline characteristics. TRIAL REGISTRATION: This meta-analysis has been retrospectively registered in Prospero (registration number: CRD42020201008).

Herpes simplex virus type 1 related acute retinal necrosis following an encephalitis illness: a case report.

BACKGROUND: Virus encephalitis is found to be a risk factor for acute retinal necrosis (ARN). CASE PRESENTATION: We herein presented a case of a 20-year-old teenage boy who suffered from encephalitis of unknown etiology with early negative pathologic results, and was primarily treated with systemic administration of high-dose steroids without antiviral therapy. He later had sudden vision loss in his right eye. Intravitreal and intravenous antiviral treatments were immediately started due to suspected ARN. Herpes simplex virus (HSV)-1 was identified later in the vitreous humor of the patient. After the surgery of retinal detachment (RD), obvious improvements in vision were observed. However, the patient had recurrent RD and vision declination 5 weeks later. CONCLUSIONS: The case with suspected viral encephalitis should be treated with antiviral therapy regardless of early virologic results in order to avoid complications of a missed viral encephalitis diagnosis, especially if systemic steroid treatment is being considered.

Does ganciclovir exert retinal toxicity after multiple continuous intravitreal injections?

BACKGROUND: The objective of this study is to report a case of acute retinal necrosis in which abnormalities in visual function did not correspond to retinal anatomical outcomes. CASE PRESENTATION: A 39-year-old female diagnosed with acute retinal necrosis underwent repeated (nine rounds) intravitreal ganciclovir injection (3 mg/0.1 ml) into the left eye, one injection every 2 weeks. During the therapy, the patient noticed her visual acuity declining gradually. The best corrected visual acuity in the left eye was 20/33. The visual field showed massive visual damage. There was no posterior necrotizing involvement, no macular edema or exudation, and only slight abnormity of the interdigitation zone in the fovea area was visible on OCT. Angio-OCT revealed normal capillary density of three retinal capillary and choriocapillaris layers. The visually evoked potential was normal. The photopic single-flash response showed a declined amplitude of a-wave and b-wave. The amplitudes of photopic 30 Hz flicker were decreased. Multifocal electroretinography revealed macular dysfunction. CONCLUSION: Ganciclovir-associated photoreceptor damage may induce abnormalities in retinal function in response to multiple continuous intravitreal ganciclovir injections at a relatively high dosage (3 mg/0.1 ml).

Association of retinal detachment with age 50 years or younger at onset in patients with acute retinal necrosis.

BACKGROUND: Due to the guarded prognosis of acute retinal necrosis (ARN), it is relevant to develop a strategy to early categorize those patients in a higher risk of worse outcomes. The purpose of this study is to describe clinical features and predictive factors for retinal detachment (RD) in patients with ARN. METHODS: Retrospective observational case series of 34 adult patients (38 eyes) with ARN examined between January 2005 and July 2015 in the National Eye Institute (Bethesda, USA), the Department of Ophthalmology, University of Chile (Santiago, Chile), and APEC (CDMX, Mexico). RESULTS: A total of 16 males and 18 females with a mean age at presentation of 44.5 ± 16.8 years were included. Twenty-seven patients (79.4%) received intravenous acyclovir as first-line treatment, and 7 patients received either oral antiviral (4 patients) or oral plus intravitreal antiviral (3 patients). All subjects were treated with prednisone, with a mean initial dose of 57.7 ± 16.3 mg per day. Seventeen patients (50.0%) developed retinal detachment. An association of retinal detachment with age at onset was observed (p = 0.04), with patients younger than 50 years presenting a higher risk (OR = 14.86, p = 0.0009). Additionally, patients in this higher risk group had more inflammation in both anterior chamber and vitreous (p = 0.04 and 0.03, respectively). No other predictive factor for retinal detachment was found in the present study. CONCLUSIONS: RD represents an important complication in patients with ARN. Younger patients may be at higher risk of this complication, possibly secondary to the presence of a higher level of inflammation.

Acute retinal necrosis caused by co-infection with multiple viruses in a natalizumab-treated patient: a case report and brief review of literature.

BACKGROUND: Acute retinal necrosis is considered a rare infectious uveitis. This condition is usually caused by varicella-zoster virus or herpes simplex virus. Acute retinal necrosis caused by co-infection with multiple viruses is extremely rare. Herein, we report a case of acute retinal necrosis caused by co-infection with herpes simplex virus (type I and II) and varicella-zoster virus (VZV) in a natalizumab-treated patient due to multiple sclerosis. CASE PRESENTATION: An adult man presented with a complaint of decreased vision of the right eye from 12 days ago. He was a known case of multiple sclerosis receiving natalizumab. Examination of the right eye revealed severe conjunctival injection, fine diffuse keratic precipitates, 3 + anterior chamber and vitreous cells, elevated intraocular pressure (26 mmHg), a blurred optic disk with hemorrhagic patches, and occlusive vasculitis plus confluent necrotizing patches in the peripheral retina compatible with diagnosis of acute retinal necrosis. He underwent anterior chamber and vitreous tap, and real-time PCR detected HSV I & II and VZV on the vitreous specimen. A second PCR showed the same result. After neurological consultation, natalizumab was discontinued and intravenous acyclovir was started followed by oral acyclovir and oral prednisolone to control the disease, which was successful. CONCLUSIONS: Although rare, multiple-viral infection should be considered in the physiopathology of acute retinal necrosis, especially in immunosuppressed patients.

Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis.

BACKGROUND: The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder. METHODS: Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed. RESULTS: VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = - 0.834). CONCLUSION: The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

A case of chronic retinal necrosis after tube shunt surgery for secondary glaucoma associated with cytomegalovirus corneal endotheliitis.

BACKGROUND: We report a case of chronic retinal necrosis (CRN) combined with cytomegalovirus (CMV) corneal endotheliitis. CASE PRESENTATION: An 80-year old man was diagnosed with CRN that developed after tube shunt surgery with vitrectomy for secondary glaucoma associated with CMV corneal endotheliitis. After the use of oral valganciclovir and panretinal photocoagulation, the retinal lesion resolved rapidly and he has maintained visual acuity better than before the onset of CRN. CONCLUSIONS: Use of oral valganciclovir, prophylactic panretinal photocoagulation for the non- perfusion area and vitrectomy were effective in maintaining the visual acuity for the patient with CRN.

Varicella zoster virus (VZV) oculomeningoencephalomyeloradiculitis: a previously undescribed constellation.

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

Visual outcome and poor prognostic factors in acute retinal necrosis syndrome.

OBJECTIVE: To evaluate the impact of selected clinical parameters on the mid-/long-term visual outcome of patients with acute retinal necrosis (ARN) DESIGN: A retrospective cohort study SETTING: Two University Hospitals (Parma, Italy; Lausanne, Switzerland). PARTICIPANTS: Thirty-nine non-HIV patients (39 eyes) with ARN, as confirmed by polymerase chain reaction on intraocular samples. The following potential predictors were tested using linear regression models: age, sex, etiology, best-corrected visual acuity (BCVA) on admission, delay between ARN symptom onset and treatment initiation, and surgery (performed or not). MAIN OUTCOME: BCVA at the final follow up RESULTS: Thirty-nine of 39 non-HIV patients (22 men and 17 women; mean age, 50 years) diagnosed with ARN were enrolled in the study. Etiologies were: varicella-zoster virus in 25 eyes (64%), herpes simplex viruses in the remaining 14 eyes. The average follow-up duration was 19 ± 13 months. All patients had undergone systemic antivirals; surgery was performed in 16 eyes. The mean delay between onset of visual symptoms and antiviral treatment initiation was 15 ± 31 days (range, 1-180 days). The mean BCVA at baseline was 0.83 ± 0.75 logMAR, while the mean final BCVA was 0.75 ± 0.81 logMAR. Both initial BCVA and treatment delay (TD) were significantly correlated with the final BCVA (p < 0.05). CONCLUSIONS: Initial BCVA and TD seem to be significant predictors of mid-/long-term visual outcome in non-HIV patients affected by ARN.

Acute retinal necrosis following dexamethasone intravitreal implant (Ozurdex®) administration in an immunocompetent adult with a history of HSV encephalitis: a case report.

BACKGROUND: Dexamethasone intravitreal implants (0.7 mg) (Ozurdex®, Allergan Inc., Madison, NJ) are FDA approved for managing macular oedema (ME) of retinal vein occlusion (RVO). The major complications associated with intravitreal Ozurdex® implant include increased intraocular pressure and cataract progression. In regard to the occurrence of retinal complications, we report an unusual intravitreal Ozurdex® implantation-related acute retinal necrosis (ARN). CASE PRESENTATION: A 45-year-old immunocompetent woman with a history of encephalitis presented with photophobia, redness, floaters, and rapidly decreased vision in her left eye. Three and six months ago, she received two doses of intravitreal Ozurdex® implant for ME of RVO. Clinical evaluation, including slit-lamp biomicroscopy, retinal photography, and fluorescein angiography, revealed anterior chamber cells, granulomatous keratic precipitates, cells in the vitreous, optic disc oedema, occlusive retinal vasculitis, scattered retinal haemorrhages, one quadrant of peripheral white areas with retinal necrosis, optic disc and vessels fluorescein staining, and retinal nonperfusion zones. All the above clinical manifestations showed an ARN. Herpes simplex virus was detected in the aqueous and vitreous humour by quantitative polymerase chain reaction testing. Intravenous acyclovir 500 mg tid for 7 days followed by oral valcyclovir was immediately performed for ARN. At 4 months, the patient's condition improved without retinal detachment, and the best-corrected visual acuity remained stable at 0.3. CONCLUSIONS: ARN might represent a risk of Ozurdex® administration.

[Retinal toxicity study of intravitreal ganciclovir in albino rabbit].

Objective: To elevated the retinal toxicity of intravitreal ganciclovir in albino rabbit eyes. Methods: Experimental study. Twenty-four New Zealand albino rabbits (forty-eight eyes) were divided into four groups by random. Three groups were prepared for ganciclovir experiment, named A, B, C. Each group received intravitreal injection ganciclovir dose at 400 µg/0.05 ml, 2 mg/0.05 ml and 5 mg/0.05 ml respectively. The other group named D served as a control accepted intravitreal injection 0.9% normal saline 0.1 ml. Before and after 1, 2 and 4 weeks, flicker full field electroretina gram (ERG) was recorded. After 1, 2 and 4 weeks light and electron microscopic tests were recorded for further toxicity study. Results: There was significant difference in amplitude of maximal combined response a wave in one week(χ(2)=8.319, P=0.04), and pairwise comparison the 5 mg group (140.50 µV) was significantly lower than the control group (165.00 µV) (χ(2)=-2.830, P=0.028). Maximal combined response b wave in four weeks(χ(2)=-10.626, P=0.014), and pairwise comparison the 5 mg group (261.50 µV) was significantly lower than the control group (398.00 µV) (χ(2)=-2.973, P=0.018). 30 Hz flicker response in one, two and four weeks(χ(2)=17.589, 8.225, 8.997, P=0.001, 0.042, 0.02), and pairwise comparison the 5 mg group (71.3µV, 106.00µV, 63.60µV) was significantly lower than the control group (118.50µV, 129.00µV, 116.50µV) (χ(2)=-4.142, -2.826, -2.713, P=0.000, 0.028, 0.040). There was no histologic retinal toxicity evidence of group 400 µg and control group observed by light microscopy in any stage of the study. Histologic changes of group 2 mg four week later, group 5 mg two and four week later include inner nuclear layer loose arranged, nuclear of ganglia were widened and outer plexiform layer stained less in four week later. By electron microscopic observation, the ultrastructure of retina changed to different degrees and became worse in each experimental group with significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors, loosely arranged and disordered in the outer segment of photoreceptors four weeks later. Conclusions: The retinal function and morphology were normal in group 400 µg. Group 2 mg and 5 mg had retinal toxicity, and 5 mg was more severe. Therefore, the clinical application of ganciclovir in the treatment of acute retinal necrosis (ARN) should select the minimum effective dose to avoid the occurrence of retinal toxicity. (Chin J Ophthalmol, 2020, 56:279-285).