EyeWorld Asia-Pacific September 2019 Issue

EWAP SEPTEMBER 2019 61 CORNEA «ÕÃià ܅i˜ `ÀÞ iÞi y>ÀiÃ] which he said occurs in the “>œÀˆÌÞ œv «>̈i˜Ìð º7…i̅iÀ ̅i «>̈i˜Ì…>à i«ˆÃœ`ˆV y>Àià and in the interval is relatively quiet or the patient is on maintenance therapy with an immunomodulator, they are }œˆ˜} ̜…>Ûi y>ÀiÃ]»…i Ã>ˆ`° º ˆŽi ̜ ÕÃi «ÕÃi ̅iÀ>«Þ ܈̅ ÃÌiÀœˆ`à ̜ VœÛiÀ ̅iÃi y>Àið» i>˜Ü…ˆi] À° *yÕ}vi`iÀ will use a steroid pulse with cyclosporine, tapering to a stop after 1 month. Patients going on short- course therapies of about 2 weeks don’t typically need a follow-up visit unless symptoms «iÀÈÃÌ œÀ y>ÀiÆ «>̈i˜Ìà œ˜ maintenance therapy will typically be seen for follow up in a month to 6 weeks by À° œÛ>˜iÈ>˜] ˆ˜ È ÜiiŽÃ LÞ À° œ>˜`° /Ài>̓i˜Ì v>ˆÕÀi ˆÃ À>ÀiÞ >˜ ˆÃÃÕipº/Þ«ˆV>Þ] steroids don’t fail,” Dr. œÛ>˜iÈ>˜ Ã>ˆ`pLÕÌ >``ˆÌˆœ˜> ̅iÀ>«ˆià œÀ >`Õ˜VÌà ÃÕV…>à punctal occlusion are considered depending on patient response. .KƂVGITCUV E[ENQURQTKPG combo? Some patients report using LœÌ…ˆwÌi}À>ÃÌ >˜` VÞVœÃ«œÀˆ˜i ̜}i̅iÀ° À° *yÕ}vi`iÀ Ã>ˆ` that while there is no evidence to support this concept, he has patients who use both and think the combination is better than monotherapy. º `œ˜½Ì ̅ˆ˜Ž ̅iÀi½Ã >˜Þ Ài> science behind whether that ܜÀŽÃ]» À° œÛ>˜iÈ>˜ Ã>ˆ`° º œÌ…>Ài /‡Vi ˆ˜…ˆLˆÌœÀÃ] Ü it’s hard to construct a logical argument that they would be highly additive to each other. Yet they are two drugs that work on the same disease, so it makes sense to try them together.” Dr. de Luise said that the two drugs do work in different places and at different points in the ˆ˜y>““>̜ÀÞ V>ÃV>`i\ ˆwÌi}À>ÃÌ on the ICAM-LFA interaction, cyclosporine on calcineurin inhibition on newly hatched /‡ViÃ° º/œ ̅i iÝÌi˜Ì ̅>Ì Ì…i dry eye in a given patient is predominantly or totally related ̜ ˆ˜y>““>̈œ˜ ܅ˆV…ˆÃ ˜œÌ always the case), there may be > ÃޘiÀ}ˆÃ̈V Li˜iwÌ Ìœ ÕȘ} both medications,” he said. º œÜiÛiÀ] ˆ˜ ̅i Ài>‡ÜœÀ` scenario, there may be insurance limitations, and using both may have to be paid out of pocket by that particular patient.” Despite anecdotal reports, À° œ>˜` `œiØ½Ì Ãii > Àœi vœÀ ̅i Vœ“Lˆ˜>̈œ˜° º v ÜiÀi to add a second medication, I would rather not put them on two drugs that work on a ȓˆ>À «>̅Ü>Þ]»…i Ã>ˆ`° º would rather add a steroid as my second medication than a drug with a similar mechanism.” New formulations ݈Ã̈˜} >˜Ìˆ‡ˆ˜y>““>̜ÀÞ agents are evolving through new formulations. º ½“ iÝVˆÌi` >LœÕÌ > ˜iÜ clinical trial on loteprednol 0.25%, which is under the study name of KPI-121 [Kala *…>À“>ViṎV>ÃR]» À° œ>˜` Ã>ˆ`° º/…ˆÃ ÌiV…˜œœ}Þ ˆÃ > nanoparticle suspension that has a mucous-penetrating property, so it penetrates the ocular surface well, and therefore, you can lower the concentration and get a better effect.” Inveltys, a 1% formulation using the proprietary AMPPLIFY mucus-penetrating particle drug delivery technology (Kala Pharmaceuticals) described LÞ À° œ>˜`]…>à >Ài>`Þ been approved by the FDA as the only twice-daily ocular corticosteroid for the treatment œv ˆ˜y>““>̈œ˜ >˜` «>ˆ˜ >vÌiÀ ocular surgery. A solution form of cyclosporine 0.09% is FDA-approved and available as Cequa (Sun Pharma). Another cyclosporine solution formulation, CyclASol 0.1% (Novaliq), is in Phase 3 clinical trials. The FDA-approved Cequa is 0.09% cyclosporine encapsulated in nanomicelles and stored in solution, delivered via classic dropperette. It’s a more potent concentration, and the micelle encapsulation allows greater tissue penetration— ºÃœ Üi ˜ii` ̜ }iÌ Vœ“vœÀÌ>Li with its tolerability in the eye,” À° œÛ>˜iÈ>˜ Ã>ˆ`° º/…iœÀïV>Þ] ̅i ˆ˜VÀi>Ãi` concentration and the formulation in solution of Cequa, which is a solution of the historically highly insoluble molecule cyclosporine, should create increased bioavailability and thus an increased patient response,” Dr. de Luise said. i>˜Ü…ˆi] º ÞVƂ-œ ˆÃ interesting because it is not a water-based drop,” Dr. œÛ>˜iÈ>˜ Ã>ˆ`° ,>̅iÀ] ̅i 0.1% concentration is delivered ˆ˜ > «iÀy՜ÀœV>ÀLœ˜ ˆµÕˆ`] Ü ºˆÌ ˆÃ «ÀœL>LÞ LiÌÌiÀ ̜iÀ>Ìi` than any other formulation of this drug on the eye,” he said. º/…>Ì Ã>ˆ`] VÞVœÃ«œÀˆ˜i ˆÃ intrinsically irritating, and dry eye disease is often a heterogenous group of both aqueous `iwVˆi˜Ì `ÀÞ iÞi `ˆÃi>Ãi >˜` evaporative dry eye disease, so it remains to be seen how effective these formulations will be as usage and experience by the ophthalmic community increases,” Dr. de Luise noted. As such, it remains to be seen how these new formulations ܈ ˆ˜yÕi˜Vi ÃÌ>˜`>À` `ÀÕ} ̅iÀ>«ˆið º ܈ iÛ>Õ>Ìi ̅i new cyclosporines and based on clinical response decide if I change my treatment paradigm œÀ ˜œÌ]» À° œ>˜` Ã>ˆ`° Dr. de Luise cited additional therapies in the pipeline: iontophoresis anti- ˆ˜y>““>̜Àˆià vÀœ“ Þi >Ìi *…>À“>Æ «iÀy՜ÀœœVÌ>˜i ˜œ˜‡ ÃÌiÀœˆ`> >˜Ìˆ‡ˆ˜y>““>̜Àˆià from Novaliq, which is exciting, he said, because there are no currently approved strategies for evaporative eye disease due to “iˆLœ“ˆ>˜ }>˜` `ÞÃv՘V̈œ˜Æ and an aldehyde trap for ÕÃi >à >˜ >˜Ìˆ‡ˆ˜y>““>̜ÀÞ from Aldeyra Therapeutics. i>˜Ü…ˆi] À° œ>˜` ˆÃ œœŽˆ˜} out for RGN-259, a thymosin beta-4-based sterile and preservative-free eye drop being developed by RegeneRx for dry eye and neurotrophic keratitis, currently in Phase 3 trials. There are still some gaps to w° º/…iÀi ˆÃ ˜ii` œv >˜ >˜Ìˆ‡ ˆ˜y>““>̜ÀÞ Ìœ ˆ˜…ˆLˆÌ VœÀ˜i> neovascularization and one to