David Maskill
Leeds, United Kingdom

At the sanctuary of Asklepios in Epidaurus, four limestone stelae preserve around seventy clinical vignettes from the fourth century BC: the Iamata (ἴαματα) or “remedies.” Pilgrims here underwent enkoimesis (ἐγκοίμησις), an incubation sleep (perhaps induced by the opium found among the sanctuary’s coffers), in which the god of medicine was said to heal them.¹ Historians have long treated these inscriptions as propaganda, warnings to skeptics, and votive offerings,² but many align with surgical practice corroborated independently.³ Iama 9, mentioning ophthalmic disease,⁴ contains uniquely strange anatomical detail.

We have, therefore, prepared a new translation and interpretation of Iama 9 (Figure 1), arguing that it preserves the earliest clinical record of symblepharon. This essay follows the one-eyed man of Epidaurus throughout history: first, the clinical evidence within the inscription itself; second, the slow verbal history by which “symblepharon” came to name what he had; and third, the two-thousand-year surgical struggle, from Heraclides to amniotic membranes, to treat it for good.

Reading the adhesions

Iama 9 describes a suppliant as ἁτερόπτιλλος, a compound of the Doric Greek for “one of two” and “eye,” or “one-eyed.”⁵ Despite this etymology, some scholars interpret it as generic monocular blindness.^6,7 The surrounding narrative, however, suggests otherwise: bystanders mock the man for daring to seek a cure at all, because his eye appears entirely absent. Previous analyses explained the account as propaganda or misattribution of vision from the unaffected eye.^4,7 There is, however, a third possibility.

Symblepharon is an adhesion of the eyelid to the conjunctiva covering the eyeball (Figure 2), eventually obliterating the fornices (the loose pockets where eyeball conjunctiva folds into eyelid conjunctiva). A related condition, ankyloblepharon, is an adhesion of lid to lid. In symblepharon’s most complete form (total symblepharon), the globe becomes invisible beneath scar tissue, while the lids remain present. Photographs in modern case reports demonstrate how this can be clinically indistinguishable from anophthalmos, the absence of an eye.^8,9 Today, symblepharon is encountered mostly as the end stage of Stevens-Johnson syndrome, chemical burns, or trachoma.¹⁰ The latter was so common in the Hippocratic era¹¹ and later antiquity¹² that its cicatricial complications were a common challenge.

Ancient physicians met this challenge head-on. The Roman encyclopedist Celsus, writing in the first century AD, describes eyelid adhesions (which he calls ancyloblepharus) and an unnamed lid-to-globe subtype (now called symblepharon) for which he recommends a specific surgical technique (careful sub-incision of the adhesion with a scalpel).¹³ He attributes this technique to Heraclides of Tarentum (third to second century BC), a Greek empiricist physician frequently cited by Galen, who trained under a follower of the great Alexandrian anatomist, Herophilus.¹⁴ This hints at a surgical tradition older than the few texts that survived, and one that continued. Paul of Aegina, in the seventh century AD, was still describing συμφυῶν βλέφαρον (“adhesion of the eyelid”) and similar surgical management.¹⁵ Al-Halabi, writing in the thirteenth century and citing seventy-three authors (including many ancient Greeks), specifies the design of rose leaf needles for the task of lid adhesiolysis.¹⁶ The idea that a fourth-century BC physician-priest could have performed at least a partial adhesiolysis to treat symblepharon is therefore not implausible.

In this context, it seems likely Iama 9 may contain the earliest record of symblepharon to date. First, the inscription identifies the presence of eyelids together with the absence of the globe. Total symblepharon is, as already described, among the few conditions that produce this appearance (differential diagnoses in Table 1). Second, the text uses the word διαγαγόντα (“having drawn apart”) for the opening of the lids, which contrasts with other ophthalmic Iamata (e.g., Iama 40, in which a remedy is simply poured into a supine suppliant’s eye), especially since this is the only instance of its use. Iama 9 is therefore more consistent with adhesions than voluntary lid closure or blepharospasm, which would typically resolve during sedation anyway. Third, since an anti-inflammatory agent can aid adhesiolysis, the mentioned φάρμακον (“drug”) may align with ancient pharmacological traditions for ophthalmic disease, such as the Paccianon recommended by Galen centuries later.¹⁷ The opium-assisted enkoimesis may also have contributed here: sedation would have made any kind of eyelid procedure considerably easier for a priest-physician working by lamplight. Last, the outcome is described by the minimal claim that the man departed “seeing with both eyes” (βλέπων ἀμφοῖν) rather than, say, a more dramatic claim of a newly created eyeball. Partial adhesiolysis clearing the visual axis could perhaps restore light-perception or hand-movements vision, which ancient observers might have characterized as “seeing.” This line also excludes congenital disease (e.g. cryptophthalmos), since this would have caused such dense amblyopia as to make restoration of any vision unlikely.

Of course, retrospective diagnoses are unfalsifiable, even if reasonably backed by appropriate scholarship.¹⁸ It is certainly feasible that Iama 9 describes an exaggerated or invented cure. But, as Celsus proves, such a cure would not have been impossible. It is therefore ironic that the dismissal by modern scholars echoes that of the ancient bystanders. In both cases, an initial impression causes the scholar/bystander to prematurely close the diagnosis before all of the evidence is fully weighed, meaning that vital information is omitted. In the clinical literature, this mistake is usually known as “anchoring bias,” and it still leads to diagnostic error in modern practice.¹⁹ In fact, so persistent is the anchoring bias, that even the word “symblepharon” itself is liable to cause it.

Naming the adhesions

The term “symblepharon” is derived from the ancient Greek, συν- (“together”) and βλέφαρον (“eyelid”), but is not itself ancient. Although frequently attributed to Ernst Fuchs’ 1892 textbook (Figure 2),^10,20 it appears in Samuel Cooper’s The First Lines of the Practice of Surgery (1819) as a description of eyelid-to-globe adhesion.²¹ An even earlier English variant, symblepharum, was defined in Robert Hooper’s Quincy’s Lexicon Medicum (1811) as a “concretion of the eyelid to the globe of the eye.”²² The true coinage likely emerged during the interval between the sixteenth and eighteenth centuries when Renaissance nosologists began Latinizing Greek medical vocabulary. Jean de Gorris’s Definitionum Medicarum (1564) used αγκυλοβλεφαρον (which he defines as “palpebrarum coharentia”) to describe all eyelid adhesions,²³ but by 1785, George Wallis’s translation of François Boissier de Sauvages’s Nosologia Methodica distinguished between ancyloblepharon and symblepharosis.²⁴ The conceptual history of symblepharon, then, turns out to be as sticky as the condition itself—and clinically sticky too, for symblepharon remains among the most challenging of ocular surface diseases to manage.

Treating the adhesions

Even Celsus noted that early symblepharon surgery rarely succeeded due to recurrence from raw wounds. But more innovative surgery would require the advent of anesthesia. Accordingly, it was in 1833 that Friedrich August von Ammon (1799–1861) proposed a two-stage solution: the adherent eyelid was excised as a triangular flap and left temporarily in place on the globe while the surrounding lid was closed over it, so that once the retained patch was removed, the lid faced healthy mucosa rather than a second raw wound.²⁵ But this helped only for the most partial cases, since it replaced no lost tissue. A full cure would require replacing the diseased conjunctiva outright. It was the Leeds surgeon Thomas Pridgin Teale, Jr. (1831–1923) who first attempted this in 1860, transplanting adjacent healthy conjunctiva over the excised area.²⁶ Where the available amount of donor conjunctiva proved insufficient, surgeons looked elsewhere: John Reisberg Wolfe (1824–1904) popularized rabbit conjunctiva,²⁷ while Karl Stellwag von Carion in 1873 Vienna first used human lip mucosa,²⁸ a technique whose success British ophthalmologists confirmed by 1889.²⁹ De Rotth went further still in 1940, using fresh fetal membranes whose growth factors spared the patient a second surgical site altogether.³⁰ Amniotic grafts were then abandoned for decades over inconsistent tissue processing, and alternatives such as skin grafting fared no better.³¹ The approach returned only when Kim and Tseng reintroduced amniotic grafts in rabbit corneas in 1995,³² followed swiftly by the first modern human amniotic membrane transplants (AMT) for ocular surface disease in 1997.³³ AMT and other mucosal grafts are now standard treatment for symblepharon and related ocular surface disease,³⁴ sometimes aided by symblepharon rings and conformers introduced in the 1950s,³⁵ though these appear to add little efficacy of their own.³⁶

Symblepharon, however, remains an unsolved problem. AMT still fails in a meaningful minority of cases: one recent series recorded recurrence in 12.2% of eyes.³⁶ Cultivated limbal epithelial transplantation is a newer, more successful strategy.³⁷ But two and a half thousand years after Iama 9, the problem Celsus described remains unresolved.

What the bystanders missed

This observation brings us to our last example of anchoring bias: both bystanders and scholars anchor on “cure” as the only acceptable outcome. For example, we might conclude that if we cannot reliably cure symblepharon today, the one-eyed man of Epidaurus was probably not cured either. But he may, on the evidence available, have been treated, which two thousand years of surgical history suggests was, and remains, the more honest goal. This is what the ancient bystanders missed in their enthusiasm to mock the suppliant: a cure is not the same as an improvement. And there is often some improvement in quality of life to be gained, even when marginal. For an eye without perception of light, even seeing hand movements is a miraculous gain. This incremental battle for sight is what has motivated ophthalmologists and their predecessors for thousands of years, and is what Iama 9, however uncertain its interpretation, may be the earliest record of.

Table 1. Differential diagnosis of apparent anophthalmos in an eye with identifiable lid structures

Condition	Lids present?	Explains anophthalmic appearance?	Permits visual recovery?
Cryptophthalmos	No (absent/fused)	Yes	No
True congenital anophthalmos	Yes	Yes	No
Sclerocornea	Yes	Partial	No
Phthisis bulbi	Yes	No (shrunken globe visible)	Very limited
Dense corneal pannus	Yes	No (cornea visible but opaque)	Very limited
Total symblepharon	Yes	Yes (cornea obliterated by adherent conjunctiva with forniceal shortening)	Yes, if partial adhesiolysis performed

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