Fig. 13.1
Anterior segment photography of a patient with acute retinal necrosis showing a mutton fat-like keratic precipitates
Fig. 13.2
(a) Peripheral retina of a patient with acute retinal necrosis showing periarterial vascular sheathing and necrotizing retinitis. (b) Fluorescein angiogram showing peripheral occlusive vasculopathy
Delayed complications of ARN may include chronic vitritis, macular edema, optic atrophy, epiretinal membrane formation, proliferative vitreoretinopathy, viral relapse with cessation of antiviral medication, and phthisis bulbi [16].
13.3 Diagnosis
In 1994, the American Uveitis Society established the standard clinical criteria for the diagnosis of ARN [17]. According to the criteria, the diagnosis of ARN syndrome should be generally based on clinical appearance and the course of infection. These criteria are (1) focal well-demarcated areas of retinal necrosis with discrete borders in the peripheral retina, (2) rapid circumferential progression of necrosis in the absence of antiviral therapy, (3) evidence of occlusive vasculopathy, and (4) prominent inflammation in the vitreous and anterior chamber. However, even with these specific diagnostic criteria, much ambiguity can still exist in assaying a definite etiology for many cases of posterior uveitis.
In the last decade, great advances have been made in the diagnosis of ARN syndrome, such as detection of viral DNA in intraocular fluids using polymerase chain reaction (PCR). PCR analysis of aqueous humor can be especially helpful and clinically important for cases of posterior uveitis of unknown etiology. In 2003, Tran et al. [18] performed PCR on aqueous humor for the detection of viral DNA in patients with necrotizing herpetic retinitis. Specific viral DNA was detected in the aqueous humor of 86.4 % of cases. Although more invasive than anterior chamber paracentesis, vitreous sampling obtained at the time of vitrectomy can also be used for the diagnosis of ARN [19].
PCR analysis of ocular fluids can also be supplemented with calculation of a Goldmann-Witmer coefficient (GWC) in the diagnosis of ARN. The GWC is a method of comparing intraocular antibody production to serum antibody production to diagnose ocular infections. The addition of a GWC to PCR can add additional diagnostic information in cryptic cases of posterior uveitis in which PCR is inconclusive [20, 21]. However, there are some drawbacks to this indirect method. Intraocular antibody production is not adequate during the early phase after onset, and therefore the GWC value cannot be calculated.
13.4 Management
13.4.1 Systemic Antiviral Therapy
After discovering the causative association between herpes viruses and ARN, the only available antiviral agent was intravenous acyclovir. The typical induction dose for intravenous acyclovir is 10–15 mg/kg given three times a day for 7–10 days. This should be followed by oral acyclovir 800 mg five times a day for 3–4 months [22–24]. Newer oral agents such as valacyclovir, famciclovir, and valganciclovir have greater bioavailability than oral acyclovir and can produce systemic concentrations nearly equal to those obtained with intravenous acyclovir [25].
13.4.2 Intravitreal Antiviral Therapy
Foscarnet is an inhibitor of viral DNA polymerase, is not dependent on viral kinases for activation, and therefore can be used against acyclovir-resistant herpes viruses. Multiple case reports describe the successful use of intravitreal foscarnet either as salvage therapy for cases of ARN not responding to standard therapy or as an adjuvant to IV acyclovir administered at the time of initial diagnosis [26, 27]. Most recently, a retrospective case series demonstrated a non-statistically significant 40 % reduction in the rate of retinal detachments in VZV-associated ARN patients treated with intravitreal foscarnet [28].
Ganciclovir can be given intravitreally or with the help of a surgically implanted device to release a sustained intravitreal concentration of 1 μg per hour over an 8-month period for patients with ARN related to CMV [29, 30].
Considering the high frequency of significant inflammation associated with ARN that contribute to the vision loss—such as moderate to severe vitritis, serous retinal detachment involving or threatening the macula, or retinitis or occlusive vasculitis involving or threatening the optic nerve or macula—it should be recommended to initiate a relatively a high dose of systemic corticosteroids (almost 1 mg/kg/day) together with antiviral drug at the onset of disease [23, 31]. The dosage of corticosteroid should be tapered in accordance with the clinical findings. Topical 1 % prednisolone acetate and a cycloplegic agent can be added to treat anterior chamber inflammation [32]. The use of oral antiplatelet agents, such as aspirin (100 mg/day), to help prevent retinal vascular occlusion has been suggested as well [23, 31], however the use of such agents remains controversial [32].
13.4.3 Prophylactic Laser Photocoagulation
The aim of prophylactic photocoagulation in ARN is to prevent retinal detachments and the associated poor visual outcomes. However, the use of photocoagulation in patients with ARN is controversial and the level of evidence supporting its use is generally weak [33]. Still, some authors believe that prophylactic laser treatment delivered posterior to active retinitis may help prevent progression to retinal detachment [34–36]. In the absence of a randomized study, the decision to apply laser must be individualized for each patient.
13.4.4 Surgery
Rhegmatogenous retinal detachment, often complicated by proliferative vitreoretinopathy, occurs in up to three-quarters of patients with ARN [34, 36–38]. When retinal detachments do occur in the setting of ARN, there are often both rhegmatogenous and tractional components, and management should address both of these contributing factors. Vitrectomy, lensectomy, endolaser, and long-acting gas or silicone oil tamponade have shown success in retinal reattachment repair and recovery of vision [39–42]. Recently, some investigators have advocated for early vitrectomy surgery in ARN patients before the appearance of a retinal detachment. Ishida et al. [42] reviewed the outcomes of patients with ARN who underwent a prophylactic vitrectomy; the surgery was not helpful in preventing detachments in eyes with posterior pole involvement. However, the rate of retinal detachment was lower in patients with mid-peripheral involvement that received the prophylactic surgery. Another study also found that early vitrectomy might prevent retinal detachments, but there was no clear benefit in the final visual outcome [41].
Compliance with Ethical Requirements Conflict of Interest The authors declare that they have no conflict of interest. Informed Consent No human studies were carried out by the authors for this article. Animal Studies No animal studies were carried out by the authors for this article.
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