Acute Retinal Necrosis: The Effects of Intravitreal Foscarnet and Virus Type on Outcome

doi:10.1016/j.ophtha.2009.08.003

Ophthalmology

Volume 117, Issue 3, March 2010, Pages 556-560

https://doi.org/10.1016/j.ophtha.2009.08.003 Get rights and content

Purpose

To study the effects of intravitreal foscarnet and the clinical differences between varicella zoster virus (VZV) and herpes simplex virus (HSV) induced acute retinal necrosis (ARN).

Design

Retrospective comparative case series.

Participants

Eighty-one eyes of 74 patients.

Methods

A retrospective case note analysis was performed in 2 tertiary referral centers.

Main Outcome Measures

Presenting and final visual acuity, and progression to retinal detachment.

Results

Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity on presentation was similar (P = 0.48), but a larger proportion had better vision (≥20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater proportion of eyes with poor vision (≤20/200) was found at the 12-month follow-up in the VZV-ARN group (60%) compared with the HSV-ARN group (35%). A greater degree of visual loss in the VZV-ARN group (0.4 logarithm of the minimum angle of resolution [logMAR]) compared with the HSV-ARN group (0.04 logMAR) was detected (P = 0.016). Retinal detachment was 2.5-fold more common in VZV-ARN (62%) compared with HSV-ARN (24%). When comparing eyes treated with (n = 56) and without (n = 25) intravitreal foscarnet, there was a 40% lower rate in retinal detachment (53.6% vs 75.0%) for VZV-ARN (P = 0.23). The numbers with HSV-ARN were too small for analysis.

Conclusions

The results support the difference of outcome in HSV-ARN and VZV-ARN. Therefore, viral identification serves as a key to predicting outcome in these patients. Intravitreal foscarnet seems to be a useful adjunct for the treatment of ARN in that it reduced rate of retinal detachment.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Section snippets

Methods

This study received ethics and institutional board approval from Guy's and St. Thomas' Hospital NHS Foundation Trust (STH) and Moorfields Eye Hospital NHS Foundation Trust (MEH). The research adhered to the tenets of the Declaration of Helsinki.

A retrospective case note review was performed at 2 tertiary referral services (St. Thomas' [EMG, MRS] and Moorfields [CEP] hospitals). All patients diagnosed with ARN from January 1994 to January 2008 were identified. Patient details including age,

Results

We identified 104 eyes with ARN (64 STH, 40 MEH) from 97 patients. Eighty-one eyes (56 STH, 25 MEH) from 76 patients had a PCR-positive diagnosis of either HSV-ARN or VZV-ARN. Bilateral ARN occurred in 4 patients with VZV-ARN and 1 patient with HSV-ARN. Sixteen eyes had no biopsy performed and PCR detected no virus in 7 eyes. Of the 16 eyes that did not have biopsies, 6 eyes (3 patients) had bilateral ARN with 2 patients presenting with simultaneous ARN and 1 patient with sequential ARN. No

Discussion

It is thought that VZV-ARN is more severe and progresses more rapidly than HSV-ARN.⁴ Our results support this conclusion with a greater risk of retinal detachment, greater degree of visual loss, and poorer visual outcome for VZV-ARN despite similar initial VA on presentation and, importantly, no difference in the area of retinitis on presentation. The cumulative proportion of eyes with VA ≥20/60 was 34.6%, which was similar to the findings of Fisher et al.¹¹ However, a greater proportion of

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Surgical Outcomes of Acute Retinal Necrosis–Related Retinal Detachment in Polymerase Chain Reaction–Positive Patients: A Single-Center Experience
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To evaluate the clinical features, operative techniques, and surgical outcomes of patients who underwent surgery for acute retinal necrosis (ARN)–related retinal detachment (RD).
Retrospective, longitudinal, consecutive case series.
Patients with polymerase chain reaction–positive ARN presenting from 2011 to 2021 who underwent vitreoretinal surgery for ARN-related RD at our institution.
Univariate, multivariate, and survival analyses were used to determine predictors of anatomic and functional outcomes.
Single-surgery anatomic success rate, recurrent RD, and visual acuity (VA) at 1 year.
Thirty-four eyes of 34 patients (32.4% women, mean age, 45.1 ± 20.4 years) were included for analysis with a median follow-up of 2.5 years (interquartile range [IQR], 0.8–5.5 years). Presenting VA was 1.1 ± 0.8 logarithm of the minimum angle of resolution (LogMAR) (Snellen ∼20/250). The median time from presentation to RD surgery was 1.7 months (IQR, 0.8–4.1 months), and the mean preoperative VA was 1.6 ± 0.8 LogMAR (Snellen ∼20/800). Small-gauge pars plana vitrectomy (PPV) with or without a scleral buckle (SB) was performed for all eyes with an overall single-surgery success rate of 63.6%, with no statistically significant differences in visual/anatomic outcomes between PPV and PPV/SB cases. Silicone oil was used for tamponade in 33 (97.1%) cases and was removed in 10 (30.3%) with good anatomic and final functional outcomes (Snellen ∼20/80). Independent predictors of recurrent RD included the female sex (hazard ratio, 8.38; 95% confidence interval, 2.03–34.68; P < 0.01) and zone 1 retinitis involvement at presentation (hazard ratio, 10.95; 95% confidence interval, 2.12–56.48; P < 0.01). The mean VA at 1 year (VA_1year) and at the final follow-up both had a Snellen equivalent of 20/640 (P > 0.05 for both compared with preoperative VA, respectively). Eyes that achieved single-surgery success had VA_1year of 20/200 versus hand movements in those with single-surgery failure (P < 0.01). On multivariate linear regression, younger age (P = 0.04) and better presenting VA (P < 0.01) were both associated with better VA_1year.
Moderate single-surgery anatomic success can be achieved with modern vitreoretinal surgical techniques for ARN-related RD, although visual outcomes remain poor. Further studies investigating interventions for increasing single-surgery success rates, for the inflammatory complications of ARN, and for preventing ARN-related RD are needed.
Risk Factors for Retinal Detachment in Acute Retinal Necrosis
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Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN.
Retrospective cohort study.
Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020.
A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN.
Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications).
Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01–5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02–1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN.
Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.
Classification Criteria for Varicella Zoster Virus Anterior Uveitis
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Citation Excerpt :
The classification criteria for VZV anterior uveitis developed herein performed reasonably well, with a low misclassification rate. VZV and HSV are causes of acute retinal necrosis syndrome, which, although primarily a retinitis, typically has anterior chamber and vitreous inflammation.28,29 Furthermore, unlike CMV retinitis, which nearly always occurs in patients with immunocompromise, acute retinal necrosis occurs in both immunologically “normal” and immunocompromised hosts.
To determine classification criteria for varicella zoster virus (VZV) anterior uveitis.
Machine learning of cases with VZV anterior uveitis and 8 other anterior uveitides.
Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set.
One thousand eighty-three cases of anterior uveitides, including 123 cases of VZV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for VZV anterior uveitis included unilateral anterior uveitis with either (1) positive aqueous humor polymerase chain reaction assay for VZV; (2) sectoral iris atrophy in a patient ≥60 years of age; or (3) concurrent or recent dermatomal herpes zoster. The misclassification rates for VZV anterior uveitis were 0.9% in the training set and 0% in the validation set, respectively.
The criteria for VZV anterior uveitis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Classification Criteria for Acute Retinal Necrosis Syndrome
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To determine classification criteria for acute retinal necrosis (ARN).
Machine learning of cases with ARN and 4 other infectious posterior uveitides / panuveitides.
Cases of infectious posterior uveitides / panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.
Eight hundred three cases of infectious posterior uveitides / panuveitides, including 186 cases of ARN, were evaluated by machine learning. Key criteria for ARN included (1) peripheral necrotizing retinitis and either (2) polymerase chain reaction assay of an intraocular fluid specimen positive for either herpes simplex virus or varicella zoster virus or (3) a characteristic clinical appearance with circumferential or confluent retinitis, retinal vascular sheathing and/or occlusion, and more than minimal vitritis. Overall accuracy for infectious posterior uveitides / panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for ARN were 15% in the training set and 11.5% in the validation set.
The criteria for ARN had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
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: Manuscript no. 2009-164.

: Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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Original articleAcute Retinal Necrosis: The Effects of Intravitreal Foscarnet and Virus Type on Outcome

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Methods

Results

Discussion

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Unilateral acute uveitis with periarteritis and detachment

Rinsho Ganka

Visual results and complications after retinal reattachment in the acute retinal necrosis syndrome: the influence of operative technique

Retina

A study of 44 patients with Kirisawa type uveitis

Nippon Ganka Gakkai Zasshi

Original article
Acute Retinal Necrosis: The Effects of Intravitreal Foscarnet and Virus Type on Outcome