Commentary: Can cryotherapy be used as an adjunct in select cases of recalcitrant endophthalmitis?

Chronic postoperative endophthalmitis is defined as infection after 6 weeks of surgery. The inflammation may persist for months. The organisms are usually indolent. Bacteria with low virulence, specifically Propionibacterium acnes, nontuberculous mycobacterium, and fungi are often isolated in chronic endophthalmitis. While the treatment is invariably on the lines of treatment for acute endophthalmitis as advocated in the Endophthalmitis Vitrectomy Study[1] more often vitrectomy, partial capsulectomy in pseudophakic eyes and explantation of the intraocular devices (such as intraocular lens, glaucoma implant) are required.

In this issue, the authors, Doshi et al., have described two cases of chronic endophthalmitis— one caused by fungus (Cladophialophora) and the other caused by Mycobacterium.[2] In absence of favorable responses to the conventional therapy of several intravitreal antibiotic injections and limited vitrectomy, the authors treated these eyes with an unconventional treatment strategy, application of cryo, while continuing with intravitreal antibiotic. Both eyes responded favorably.

The known benefits of cryotherapy date back to 2500 BC.[3] In modern medicine, Arnott first used cryotherapy for destruction of tumor.[4] It has been a long journey from use of crushed ice then to liquid nitrogen today. The mechanism of action in cryotherapy is by heat transfer, cell injury, and inflammation. Living tissue respond to extremely cold temperatures through ice formation, both within the cells and in the extracellular fluid surrounding the cells. The ice formation within small blood vessels interrupts the blood supply to adjacent cells. The living tissue is destroyed through ischemic necrosis and cell death induces inflammation. Cryotherapy has been used extensively for intracapsular cataract extraction in 1960s[5] and a randomized clinical study has shown benefits of its use in babies with retinopathy of prematurity (ROP),[6] but currently it is mostly replaced by phacoemulsification and intraocular lens implantation for cataract surgery and laser photocoagulation in case of ROP. However, cryo is continued to be used for surface eye cancers (tissue necrosis), uncontrolled glaucoma (cyclodestruction), and retinal detachments (retinopexy).[789] Use of cryo in recalcitrant pars planitis and intermediate uveitis is less often mentioned though it is recommended even as a primary treatment in eyes with snow banking.[10] In pars planitis, cryotherapy works through destruction of the inflammatory cells. The same mechanism could be attributed to the favorable outcomes in the reported two cases of chronic endophthalmitis.

A natural question would be if one could recommend cryotherapy as the standard of care in primary treatment of chronic endophthalmitis. Currently, there are not enough evidences to recommend such a treatment strategy. Possibly, one could consider this therapy in recalcitrant cases after the conventional care of intravitreal antibiotics injection and vitrectomy fail to elicit a favorable response. However, in the absence of larger case series, we do not know the ideal time to switch to this new therapeutic strategy.