Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.

Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.

[Eye-drops from olden times to the XIXth century]. / Los colirios desde la antigüedad hasta el siglo XIX.

The Spanish word "colirio" comes from the Latin collyrium, which in turn came from the Greek kollirion. Initially, the Romans use this word in a general way, but due to their use mainly in ophthalmology, the use of the term became restricted to those topical medications destined for the care and prevention of ocular diseases, from solutions and suspensions to poultices, salves and ointments. During the Middle Ages "colirio" included not only substances used to dilate ladies' pupils for aesthetic reasons but also medications for ocular hygiene and treatment. The Industrial Revolution of the XIXth century barely modified ophthalmic pharmaceutical technology. It is only since the World War II that the preparation of eye-drops has undergone a rapid development and improvement, adopting the concept of sterility as a necessary condition for all ophthalmic solutions and taking very precise rules for their elaboration and conditioning from different pharmacopeia.

Los colirios desde la antigüedad hasta el siglo XIX / Eye-drops form olden times to the XIXth century

Una de las formas farmacéuticas más utilizadas y populares en todas las épocas han sido los colirios, aunque el significado de este término ha evolucionado con l tiempo, debido principalmente a que el concepto de forma farmacéutica es relativamente reciente y a que el nombre de colirio ha servicio para denominar, en muchas ocasiones, preparados galénicos que agrupaban diferentes formas de administración. En épocas anteriores a la romana se designó con un mismo nombre a los preparados de administración ocular y a aquellos otros que se aplicaban en diversas cavidades naturales del cuerpo, así como en fístulas y heridas accidentales, en todos estos casos te utilizaban drogas de origen animal, mineral o vegetal en forma sólida, líquida o pulverulenta. La historia de los colirios, desde el Antiguo Egipto hasta el siglo XIX, permite realizar un recorrido por la farmacopea de diferentes civilizaciones y mostrar los recursos terapéuticos de cada época y su relación con la fisiopatología (AU)

The Spanish Word 'colirio' comes from the Latin collyrium, which in turn came from the Greek kollirion. Initially, the Romans use this word in a general way, but due to their use mainly in ophthalmology, the use of the term became restricted to those topical medications destined for the care and prevention of ocular diseases, form solutions and suspensions to poultices, salves and ointments. During the Middle Ages 'colirio' included not only substances used to dilate ladies´pupils for aesthetic reasons but also medications for ocular hygiene and treatment. The Industrial Revolution of the XIXth century barely modified ophthalmic pharmaceutical technology. It is only since the World War II that the preparation of eye-drops has undergone a rapid development and improvement, adopting the concept of sterility as a necessary condition for all ophthalmic solutions and taking very precise rules for their elaboration and conditioning from different pharmacopeia (AU)

Collyrium names attested on stone tablets: the example of the Helvetian corpus.

Collyrium-stamps are usually parallelepipedic stones that might have been used in the Roman world, between the second part of the first century and the fourth century A.D., to stamp eye medicine. On their four narrow sides, those seals contain instructions engraved in retrograde characters, of varying drawing quality, sometimes in Greek, mostly in Latin and in an abbreviated form. These markings represent some sort of medical prescriptions since they contain one or more of the following information: a personal name in the genitive case, a collyrium name, therapeutic instructions, and a method of administration. Like personal names and therapeutic instructions, collyrium names suggest that Roman eye medicine was inscribed in the Greek medical tradition. A comparison between the collyrium names engraved on the seals unearthed in Switzerland and the collyrium names known through our reading the Greek medical texts allows for an estimation of the influence of Greek ophthalmology on Roman eye medicine.

Collyria seals in the Roman Empire.

Roman seals associated with collyria (Latin expression for eye drops/washes and lotions for eye maintenance) provide valuable information about eye care in the antiquity. These small, usually stone-made pieces bore engravings with the names of eye doctors and also the collyria used to treat an eye disease. The collyria seals have been found all over the Roman empire and Celtic territories in particular and were usually associated with military camps. In Hispania (Iberian Peninsula), only three collyria seals have been found. These findings speak about eye care in this ancient Roman province as well as about of the life of the time. This article takes a look at the utility and social significance of the collyria seals and seeks to give an insight in the ophthalmological practice of in the Roman Empire.

Allergic conjunctivitis: the evolution of therapeutic options.

The eye has become the target of intense pharmacologic development because it represents one of the most active sites of allergic inflammation, due to it having no mechanical barrier to prevent the impact of allergens such as pollen on its surface. Over the past 20 years, we have witnessed an astonishing growth in therapeutic advances, ranging essentially from derivatives of simple aspirin to various newly developed biological immunomodulatory agents, using implantable drug delivery devices that exceed the safety and efficacy of those available for other organ systems and resorting to advanced surgical techniques for the correction of sight-threatening, disease-related complications. Overall, with the expanding knowledge base, the intricacy of ocular inflammation appears to be becoming ever more manageable and the clinical allergist/immunologist has an increasing role in the treatment outcomes of patients with anterior inflammatory disorders of the ocular surface primarily allergic conjunctivitis but also including dry eye syndromes.