Determinants of outcomes of adenoviral keratoconjunctivitis

01 Pubblicazione su rivista
Lee Cecilia S., Lee Aaron Y., Akileswaran Lakshmi, Stroman David, Najafi-Tagol Kathryn, Kleiboeker Steve, Chodosh James, Magaret Amalia, Wald Anna, Van Gelder Russell N., Bonini Stefano, Lambiase Alessandro, Rama Paolo, Messmer Elisabeth, Aragona Pasquale, Geerling Gerd, Mastropasqua Leonardo, Mencucci Rita, Dart John, Leonardi Andrea, Montero Jesus, Rolando Maurizio, Reinhard Thomas, Cursiefen Claus, Etxebarria Jaime, Gabison Eric, Szaflik Jacek P., Borderie Vincent, De La Paz Maria, Sainz de la Maza Maite, Wylegala Edward, Figueiredo Francisco, Fogagnolo Paolo, Hossain Parwez, Lorenz Katrin, Robert Pierre-Yves, Benitez del Castillo José, Creuzot-Garcher Catherine, Kruse Friedrich, Malecaze François, Merayo-Lloves Jesús, Rauz Saaeha, Alio Jorge, Carley Fiona, Kanna Ramaesh, Koppen Carina, Nemeth Janos, Murta Joaquim Neto, Torrao Luis
ISSN: 0161-6420

Purpose: To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. Design: Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). Participants: Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. Methods: Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. Main Outcome Measures: The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. Results: Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non–adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. Conclusions: A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non–adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.

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