Isaamuddin Alvi

Introduction

Acute Retinal Necrosis (ARN) and Progressive Outer Retinal Necrosis (PORN) are two major clinical entities of necrotising herpetic retinitis, a severe and vision-threatening condition caused by herpes viruses. Both conditions lead to rapid retinal necrosis, but they differ significantly in their affected populations, clinical presentations, inflammatory responses, and prognoses. Understanding these differences is crucial for early diagnosis, appropriate treatment, and vision preservation (1).

Comparison of ARN and PORN

Feature	Acute Retinal Necrosis (ARN)	Progressive Outer Retinal Necrosis (PORN)
Aetiology	Varicella-Zoster Virus (VZV) (most common), Herpes Simplex Virus (HSV-1, HSV-2), rarely Cytomegalovirus (CMV) (2)	Varicella-Zoster Virus (VZV) (most common), Herpes Simplex Virus (HSV) (3)
Patient Population	Immunocompetent and immunocompromised individuals (2)	Severely immunocompromised patients, especially AIDS (CD4 < 50), transplant recipients, and chemotherapy patients (3)
Clinical Course	Subacute onset, rapid but not as fulminant as PORN (2)	Extremely aggressive, fulminant, and often bilateral (3)
Location of Necrosis	Starts in the peripheral retina, and spreads centrally (2)	Multifocal patches of outer retinal necrosis, often posterior pole involvement early (3)
Inflammation	Severe vitritis and anterior chamber inflammation (2)	Minimal vitritis, despite extensive retinal necrosis (3)
Retinal Vasculitis	Prominent retinal vasculitis, arteriolar occlusion, and perivascular necrosis (2)	Minimal or absent vasculitis (3)
Retinal Haemorrhages	Mild-to-moderate haemorrhages in areas of necrosis (2)	Absent or mild haemorrhages, retina appears “moth-eaten” (3)
Retinal Detachment	Common (~50-75%), usually within weeks (2)	Very common, often occurring within days to weeks (3)
Response to Antivirals	Good response if treated early with IV/oral antivirals and intravitreal injections (2)	Poor response; rapid progression even with aggressive therapy (3)
Prognosis	Better prognosis if treated early; vision loss depends on retinal detachment (2)	Extremely poor prognosis, high risk of bilateral blindness (3)

Aetiology and Patient Demographics

Both ARN and PORN are caused by herpes viruses, particularly Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV-1, HSV-2). ARN can occur in both immunocompetent and immunocompromised individuals, with a higher incidence in young and middle-aged adults (4). In contrast, PORN is almost exclusively seen in severely immunocompromised patients, such as those with AIDS, transplant recipients, or cancer patients undergoing chemotherapy (5). In severely immunocompromised individuals, Cytomegalovirus (CMV) retinitis is more common than ARN, but it can still present in rare cases. The differing immune status of affected individuals may explain the varying degrees of inflammation seen in these conditions (3).

Clinical Presentation and Pathophysiology

ARN typically begins as peripheral retinal necrosis that gradually spreads toward the posterior pole. It is characterised by perivascular necrosis and retinal arteritis, leading to significant intraocular inflammation (2). In contrast, PORN manifests as multifocal outer retinal necrosis and often spares the vasculature initially (3). This distinction is critical, as ARN is associated with severe vitritis and anterior chamber inflammation, whereas PORN exhibits minimal vitritis despite extensive necrosis (3). The immune-privileged nature of the retina may also contribute to the aggressive nature of PORN in immunocompromised patients (6,7).

The risk of retinal detachment is high in both conditions. ARN has an approximately 75% risk of retinal detachment due to inflammatory changes and vitreous traction, while PORN carries an even higher risk, often progressing bilaterally within weeks. The rapid disease course in PORN makes early intervention particularly challenging (6,7).

Diagnosis and Imaging

Fundoscopic examination reveals key differences between the two conditions. ARN typically presents with confluent areas of peripheral necrosis and perivascular whitening, often with associated retinal arteritis. In contrast, PORN presents with multifocal outer retinal necrosis, which often lacks significant haemorrhage (8).

Imaging techniques such as Optical Coherence Tomography (OCT) can further differentiate the two. In ARN, OCT findings reveal inner retinal necrosis along with signs of vascular occlusion, while in PORN, outer retinal atrophy and photoreceptor layer loss are prominent. Fluorescein Angiography also provides valuable diagnostic information; ARN typically shows vascular leakage and occlusion, whereas PORN exhibits minimal vascular leakage due to the absence of vasculitis (9,10).

For definitive diagnosis, Polymerase Chain Reaction (PCR) analysis of aqueous or vitreous fluid can confirm the presence of herpesvirus DNA, allowing targeted antiviral therapy (11).

Treatment and Prognosis

The treatment approach for ARN and PORN revolves around antiviral therapy, but their responses to treatment differ significantly. ARN generally responds well to systemic IV aciclovir or oral valaciclovir, and in severe cases, intravitreal foscarnet or ganciclovir may be administered to improve local antiviral penetration (12). In PORN, systemic antivirals alone are insufficient due to poor penetration into the affected retina. Therefore, aggressive intravitreal antiviral therapy is necessary, but even with prompt treatment, PORN often shows poor response and rapid progression (13).

Adjunctive therapies can play a role in managing these conditions. In ARN, corticosteroids may be administered after antiviral therapy is initiated to reduce inflammation, but they must be used cautiously in PORN to avoid exacerbating viral replication (1). Laser photocoagulation is often employed to prevent retinal detachment in ARN but is less effective in PORN due to the rapid progression of necrosis (14). Vitrectomy is frequently required in both conditions if retinal detachment occurs (15).

The prognosis for these conditions varies dramatically. ARN has a better prognosis if treated early, though complications such as retinal detachment can still result in significant vision loss. PORN, however, carries a poorer prognosis, with high rates of bilateral blindness despite aggressive intervention. The lack of inflammation in PORN paradoxically worsens outcomes, as the immune system fails to mount an adequate response against the virus (2,3).

Conclusion

While ARN and PORN share a common viral aetiology, they differ significantly in pathophysiology, inflammatory response, and prognosis. ARN occurs in both immunocompetent and immunocompromised individuals, is characterized by severe inflammation, and generally responds better to antiviral therapy. PORN, on the other hand, primarily affects severely immunocompromised patients, exhibits minimal inflammation, and progresses aggressively, often leading to bilateral blindness.

Early differentiation and aggressive treatment are essential in preventing irreversible vision loss. Future research should focus on improving antiviral penetration and optimizing early detection strategies, particularly for high-risk immunocompromised patients.

References

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