To determine the general risk and the prognostic factors of postherpetic neuralgia and focal sensory denervation in ophthalmic zoster disease. A prospective clinical study. An ophthalmic practice participating in an eye-care network. A cohort of 81 immunocompetent adult patients with herpes zoster ophthalmicus and referred by their general practitioner during the acute phase of the disease. Various acute phase clinical parameters were determined via patient history and regular ophthalmic examinations. At a 2-month follow-up, the intensity of postherpetic neuralgia, rated on a 4-point verbal scale, and focal sensory denervation was determined. Skin tactile sensation within the ophthalmic dermatomes was tested with use of a cotton-wool tip, and corneal sensitivity was measured with use of a Cochet-Bonnet esthesiometer by comparing each eye. Statistical analysis was performed via chi2 analysis or Fisher exact test to identify prognostic factors of postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. At a 2-month follow-up, pain of varying intensity was reported by 38 participants (47%). Of these patients, 25 patients (31%) rated their pain as mild, 8 patients (10%) rated their pain as moderate pain, and 5 patients (6%) rated their pain as severe. At that time, focal loss of normal skin or corneal sensation was detected in 49 patients (60%). Patient age, acute neuralgia score, manifestation and extent of acute skin rash, signs of ocular inflammation, and nontrigeminal cranial nerve involvement were all associated with prolonged pain and tactile sensory loss. The severity of acute skin rash, based on a specific manifestation of cutaneous herpes zoster eruptions, and the extent of infection to other neural pathways were clearly associated with postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. These findings suggest that the inability of the immune system to control the spread of replicating varicella-zoster virus in the initial phase of the disease is an important factor in the pathogenesis of chronic zoster-related neuropathy.