Cornea research update

CXL-assisted infection reduction: a randomised clinical trial evaluating the effect of adjuvant CXL on outcomes in fungal keratitis

Prajna NV, Radhakrishnan N, Lalitha P, Austin A, Ray KJ, Keenan JD, Porco TC, Lietman TM, Rose-Nussbaumer J.

Ophthalmology 2020 Feb;127(2):159-166


Design: Randomised control trial of 403 patients with smear-positive filamentous fungal keratitis. Eyes were randomised to one of four treatment arms: (1) topical natamycin 5% alone; (2) topical natamycin 5% plus cross-linking (CXL); (3) topical amphotericin B 0.15% alone; or (4) topical amphotericin B 0.15% plus CXL.


Outcome: There was no difference in culture positivity 24 hours after commencing treatment between those randomised to amphotericin or natamycin, regardless of whether they received CXL. Those that received CXL had worse visual acuity (VA) outcomes: best corrected VA was 0.22 logMAR (2.2 Snellen lines) worse at three weeks and 0.32 logMAR (3.2 Snellen lines) worse at three months. There was no difference in infiltrate, scar size or adverse events between the groups.


Limitations: This study was performed in India, where there is a high incidence of fungal keratitis often associated with agricultural exposure. The spectrum of organisms responsible for fungal keratitis in New Zealand and other developed countries may be different and exhibit dissimilar response patterns to treatment. As the study included eyes with fungal keratitis due to multiple filamentous organisms, only small numbers of individual fungi were included making it difficult to detect the presence of a benefit for CXL for any particular organism.


Comment: Fungal keratitis remains a challenging condition to manage. Despite the recent interest in CXL as a treatment option in microbial keratitis, this article suggests there is no benefit in using adjuvant CXL in the treatment of filamentous fungal keratitis and it may result in worse visual outcomes.



Efficacy of amniotic membrane transplantation for the treatment of corneal ulcers

Schuerch K, Baeriswyl A, Frueh BE, Tappeiner C

Cornea 2020 Apr;39(4):479-483


Design: Retrospective analysis of 149 patients treated with amniotic membrane transplantation (AMTX) for refractory corneal ulcers. The underlying cause of the ulcers were diverse, including herpetic, bacterial and rheumatic disease, previous corneal surgery, bullous keratopathy, limbal stem cell deficiency and neurotrophic ulcers.


Outcome: The mean duration between ulcer onset and AMTX was 42 ±46 days. However, it occurred much earlier for cases following chemical injury (mean 14 days) compared to bacterial keratitis (mean 65 days). In 70% of cases, a single AMTX was sufficient to achieve epithelial closure: 21% within the first month, 40% within one to three months and 9% within three to six months. Epithelial closure was also achieved in 41% and 40% respectively of those undergoing a second and third AMTX. The highest epithelial closure rates were found in neurotrophic, herpetic and bacterial ulcers (93%, 85% and 80% respectively). The lowest success rates were found in ulcers after corneal surgery or associated with rheumatic disease (52% and 57% respectively).


Limitations: This was a retrospective study with no control group.


Comment: Amniotic membranes contain a high concentration of fibroblast growth factors and cytokines. It forms a mechanical barrier and promotes epithelial recovery while suppressing inflammation. It offers a valuable treatment option to promote corneal epithelial healing in refractory ulcers particularly neurotrophic, herpetic and bacterial ulcers. Even if not initially successful, a second or even third AMTX may result in epithelial healing.



A case-control study of keratoconus risk factors

Moran S, Gomez L, Zuber K, Gatinel D.

Cornea 2020 Jun;39(6):697-701


Design: Single centre, prospective case control study evaluating 202 patients with keratoconus and 355 controls. Patients were surveyed regarding their ophthalmic and medical histories and data regarding multiple variables was gathered and analysed.


Outcome: After multivariate analysis, the following factors showed significant results: eye rubbing with knuckles or fingertips, history of dry eye, male sex, night-time work, increased screen time, prone and side sleep position were all associated with keratoconus. Conversely, sleeping supine was found to be a protective factor. No link was found between a family history of keratoconus and development of the condition.


Limitations: Most of the data required for this study was reliant on patients’ history which is dependent on patient recollection and subject to recall bias, and there was a relatively small number of patients included.


Comment: The high prevalence of keratoconus in New Zealand is well known. Despite great improvements in diagnosis and management in recent years, the underlying pathogenesis is still a subject of debate. Eye rubbing has long been implicated as an exogenous environmental factor in the development of keratoconus, however this study also implicates other associations including sleep position, night-time work and screen time. These associations may merit further investigations and may guide future advice to patients at risk.


Dr Verona Botha is a senior ophthalmology registrar at Waikato District Health Board with a special interest in cornea and oculoplastics.


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