Comment
Bridging the knowledge gap for ocular surface squamous
neoplasia: Africa and beyond
Ocular surface squamous neoplasia (OSSN) has emerged
as an important manifestation of the HIV epidemic,
especially in sub-Saharan Africa.1 This region has not
only gained the unenviable position of having the
highest prevalence of OSSN, but patients with HIV
tend to present with larger tumours and have a poorer
prognosis.2 The many factors that may contribute to
these important features, such as co-existing human
papillomavirus infection, immunosuppression, delayed
access to care, and ultraviolet radiation exposure, may
also influence the response to therapy.
The care providers who are tasked with making
evidence-based treatment decisions must often
apply the results of studies performed in dissimilar
populations, then filter the therapeutic options through
the narrow sieve of what is locally feasible. A previous
Cochrane review found a paucity of level I or II evidence
for the treatment of OSSN in patients with HIV.3 In
The Lancet Global Health, Gichuhi and colleagues4 provide
helpful information to guide the care of individual
patients with OSSN, as well as informing those who may
influence allocation of resources and future research.
Their study fills an important knowledge gap. A readily
available topical ophthalmic medication, 5-fluorouracil,
was found to decrease the risk of recurrence after
excision from 36·2% to 10·6% when compared to
placebo. At first glance, the specific regimen may be
questioned: why was cryotherapy not employed? Why
study 5-fluorouracil when other topical agents, such as
interferon alfa-2b and mitomycin-C, are more widely
used among corneal specialists in developed nations?
The answers to these questions highlight the importance
of this study and others in delineating the best practices
for OSSN in sub-Saharan Africa and beyond.
Recurrence of disease after surgical excision has been
described in many regions; however, care must be
taken when extrapolating the literature from North
American, European, and Australian populations. While
the risk factors for recurrence have been reasonably well
defined in those typically older, male, white patients,
our understanding of OSSN in the frequently younger,
HIV-positive patient from Africa is incomplete. At
first glance, the recurrence reported in Gichuhi and
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colleagues study appears higher than in other series;5,6 See Articles page e378
what factors contribute to this finding remain to be
determined. The disease itself may carry an intrinsically
higher risk of recurrence in this population, and the
limited availability of cryotherapy to the excision
margins may contribute as well.7 Gichuhi and colleagues
point out that cryotherapy is not readily available in
the region. However, even in developed countries,
there are few prospective, randomised trials comparing
the evolving combinations of surgical techniques and
adjuvant chemotherapeutic agents. The ideal approach
to OSSN has not yet been defined in any population, and
the wide range of reported outcomes mandates that
randomised controlled trials are necessary to effectively
answer these questions. However, the available evidence
supports the efficacy of cryotherapy in reducing
recurrence after surgical excision. Opportunities
for research and programme development include
evaluating the cost-effectiveness of cryotherapy
compared to other adjuvants, such as 5-fluorouracil.
Adjuvant chemotherapy, either at the time of
surgery or postoperatively, has generally been found
to decrease the risk of recurrence.8 Interferon alfa-2b,
mitomycin-C, and 5-fluorouracil have all been reported
as efficacious. Interferon has gained popularity, both as
an empirical monotherapy, and as an additional therapy
after surgical excision.9 However, several characteristics
of this medication limit its usefulness in sub-Saharan
Africa. Cost is a paramount barrier; although the cost of
interferon medical therapy was found to be comparable
to surgery in one comparison,10 that study was based on
Medicare-allowable charges for surgery and medication
in the USA, which may not be directly applicable to
developing regions. It is also important to recognise that
interferon is a protein that must be kept refrigerated
to remain stable. This likely limits its usefulness in
developing countries. Mitomycin would then seem to
be a rational alternative; while it has been surpassed in
popularity by interferon, there are a multitude of studies
supporting the efficacy of this agent as monotherapy,
or in addition to surgical excision. However,
storage at room temperature is not recommended.
5-fluorouracil solution appears to remain stable without
e347
 Comment
refrigeration,11 and its general availability is encouraged
by its place on the World Health Organization’s list of
essential medicines.
Studies that specifically address reducing the risk of
recurrence in this population are welcome, and when
viewed through the lens of pharmacoeconomics,
provide vital guidance for health policy and the care
of individual patients. Directions for future research
include additional comparative trials of the efficacy,
safety, and cost-effectiveness of surgery compared to
topical chemotherapy alone, and continued efforts to
improve access to effective care.
Donald U Stone
Wilmer Eye Institute of Johns Hopkins University, King Khaled Eye
Specialist Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia
dstone25@jhmi.edu
I declare no competing interests.
Copyright © Stone. Open Access article distributed under the terms of CC BY.
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