THE ROLE OF THE IN THE HEALING OF CORNEAL WOUNDS*

BY Robert C. Drews, MD

INTRODUCTION WHILE THERE IS A VOLUMINOUS LITERATURE ON THE HEALING OF CORNEAL wounds,'14 the literature on the healingofiris wounds is extremely small5 6: indeed, it has been held traditionally that iris wounds do not heal.7'0 Many papers report the formation ofiris-corneal synechia, but most simply note its incidence and effect on intraocular pressure11; only afewconsider, more than trivially, the process of synechia formation and the effect of the synechia on corneal wound healing.12"13 Careful observation and recording ofevents at surgery, combined with a detailed and correlated analysis ofthe postoperative course, have permit- ted insight into the problems ofhealing ofthe posterior layers ofthe come- al wound, the role that the iris can play in this process, and surgical approaches to optimize healing based on this knowledge. This thesis analyzes the problem using the following outline:

I. Events in posterior corneal wound formation A. Penetration of Descemet's membrane vs knife sharpness B. Scissors wound formation C. Immediate changes: elastic D. Delayed changes 1. Swelling 2. Inflammation 3. Hemorrhage E. Alteration of wound shape by wound repair 1. Unsutured wounds 2. Superficial suturing 3. Deep suturing II. Wounding of the iris A. Inadvertent violation by sharp instruments *From the Department of , Washington University School of Medicine, St. Louis. TR. AM. OPHTH. SOC. Vol. LXXVII, 1979 Wound Healing 423 B. Iridotomy C. Iridectomy D. E. Blunt (forceps) 1. Crush 2. Tear 3. Massage III. Effects of the open corneal wound A. Stromal edema B. Chronic irritation C. Irregular D. Blebs E. Flat chamber F. Improper repair 1. Duplication of Descemet's membrane 2. Fibrous ingrowth 3. Epithelial downgrowth IV. Synechia formation A. Touch 1. Mechanical factors a. Fraying b. Iridodialysis c. Leak 2. Physiologic glues a. Blood b. Exudate c. Inflammation B. Scaffolds 1. Vitreous 2. Organized blood and exudates 3. Iris C. Results 1. Distortion 2. Wound () integrity D. V. Prevention of peripheral anterior synechia A. Anterior entry of the internal corneal wound B. Proper wound closure 1. Microsurgical control 2. Deep appositional sutures 4324 Drews 3. Retrospective gonioscopy C. Intact iris surface D. Wound toilette E. Intact vitreous face F. Hemorrhage G. Inflammation H. Stable iris plane 1. Extracapsular extraction 2. Intraocular VI. Consequences of anterior synechia prevention A. Benefits of prevention B. Benefits of synechiae

EXPERIMENTAL METHOD Each of the series of patients in this study consisted of consecutively performed cases. The series vary in size: at the time that a given statistic was satisfactory, the effort to keep track of consecutive cases was discon- tinued. All these questions did not arise at the same time, and the collec- tion of data on some points was begun much later than that on others. Where data did not exist, retrospective series have been constructed and analyzed. Such uniformity as exists in the series reported here results from the fact that all patients were operated on by a single surgeon, whose basic techniques have remained unaltered for almost 20 years.14 The vast major- ity of were delivered intracapsularly with erysiphake through a 1700 to 1800 wound. Wound closure has always been based on three silk track sutures.15 The silk suture size has been reduced from 6-0 stepwise to 8-0, but even this has remained standard for the last ten years. The addition ofnylon sutures to the wound was begun four years ago; prior to that time, additional sutures were either silk or collagen. The use of the operating microscope became standard ten years ago: it was previously used only in special surgical tasks and not in routine cataract surgery. Except where specifically noted, all patients reported in this paper were operated on during the last ten years. The data used in this report were collected by means oflog books, which always signifies that a case or two may not have been recorded. Hopefully, in the future all data concerning a patient will be entered directly into a computer to minimize entry errors and omissions. Such a system would include immediate computer query ofthe investigator, while the patient is being seen, concerning data which was inadvertently omitted. Wound Healing 425 Another possible criticism of the data in this study is that, with the exception of the gonioscopy study, all data were gathered by the same person acting as surgeon, observer, and author. By drawing together such a diversity ofmaterial on this single problem, additional insight has been gained into the-role ofthe iris in the healing of corneal wounds.

I. EVENTS IN POSTERIOR CORNEAL WOUND FORMATION

PENETRATION OF DESCEMETS MEMBRANE VS KNIFE SHARPNESS The special characteristics ofthe formation ofthe posterior corneal wound are almost completely dependent upon the interaction between the cutting characteristics of the perforating object and the elastic properties of De- scemet's membrane. The posterior layers of the corneal stroma do not differ significantly from the anterior fibers, and the corneal endothelium offers no barrier to penetration. The application ofaforce against tissue first results in tissue compression and deformity. The term "compression" as applied to tissues must be used with some understanding: the tissues with which we are concerned may be considered a mechanical scaffolding that supports and positions water. Water is not compressible, and the nonaqueous portions ofthe scaffolding are more easily molded than compressed. The apparent compression of most tissues, therefore, is not so much a significant loss of volume as a hydraulic displacement oftissue boundaries and fluid content. The tissue pressures developed mostly represent resistance ofthe tissue boundaries to deformation. Entry through the with a knife is ordinarily accompanied by an inward bowing ofthe stroma locally. As the knife progresses, this bowing is transmitted through the deeper layers of the stroma to Descemet's mem- brane and the endothelium (Fig 1). The amount of bowing depends on the sharpness ofthe knife edge, the rigidity of the tissues, and the . A knife of perfect sharpness would penetrate the tissues with no deformation. The deeper the groove, the less support the remaining layers ofthe cornea receive from the overlying stroma, and the more dependent the knife is on intraocular pressure to hold the tissues against it. A soft is extremely difficult to perforate. The diamond knife begins its penetration almost perfectly. The wedge shape of its body, however, impedes its progress, requiring a horizontal displacement of the tissues (Table I). In contrast, the exquisitely sharp Superblade (Medical Workshop) enters the tissue with almost as little A96 Drews resistance as the diamond knife. Its extreme thinness (90,) allows little tissue distortion, and this blade may slip into the anterior chamber even in an eye with less than 5 mm Hg pressure. With intraocular pressures above 10 mm Hg, it is often unnecessary to fixate the globe in order to penetrate the cornea with this knife. Scanning electron micrographs show the edge properties that give this blade its superior cutting qualities (Fig 2). With knives of less sharpness, penetration of Descemet's membrane

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FIGURE 1 Tissue support against knife penetrating cornea into anterior chamber includes rigidity of stroma, elastic support of Descemet's membrane, and opposing intraocular pressure. Wound Healing 427

TABLE I: COMPARISON OF KNIVES BLADE ANGLE CROSS SECTION THICKNESS Diamond Knife Old 450 2.0 mm New 45° 0.3 mm Keratome 10±0 0.36 mm Superblade 100 0.09 mm becomes an increasing challenge. Observed under the operating micro- scope both directly and with gonioscopy, Descemet's membrane can be seen to move before the knife blade. The more oblique the approach, the less the vector of force perpendicular to Descemet's membrane and the greater the vector parallel to its surface. The more shelving the wound, the more perfect the point must be to perforate. Stripping of Descemet's membrane may result as the point pushes the membrane ahead of it centrally rather than penetrating cleanly. The deepening ofagroove with a conventional Beaver or Bard Parker blade may result in excessive shelving of the internal layers, as the opened groove deprives the deeper tissues of support, allowing them to bow away from the knife. One ofthe reasons for the superior action ofthe keratome and Superblade is that the thin blades permit collapse ofthe tissues over the knife, lending support to the deeper layers as the initial perforation is made. With an operating microscope it is possible to see Descemet's membrane carried forward in front ofa defective knife tip. As the deformity increases, both increasing tissue resistance is met and increasing intraocular pressure is achieved, with increasing tissue support until the cutting pressure ofthe knife tip forces entry. _.S

....

FICURE 2 Medical Workshop Superblade. Remarkable smoothness seen accounts for its superior pene- trating and cutting properties. A: X 28. B: X 390. A28 Drews Knives cut most effectively when there is relative motion between the knife blade and the tissue. Even a razor can be pressed fairly firmly against the palm of the hand without cutting, but if the slightest motion is im- parted, the blade slices rapidly through the tissue. The action of a knife point and the edge of the blade are different for this reason. The point's action depends on maximizing pressure (force per unit area) by minimizing the effective area of the tip. The edge of a blade cuts by slicing. Once a stretched Descemet's membrane is perforated, the recoiling membrane slices along the knife or keratome blade easily. Observation of the entrance of the keratome into the anterior chamber by gonioscopy, or direct observation ofthe blade from the interiorofan eye that has been sectioned and inverted under the operating microscope, reveals two separate events. The tip ofa dull keratome bears a small mound of Descemet's membrane in front ofit, torn free ofthe underlying stroma. The size of this mound decreases rapidly as keratome tip sharpness in- creases. With the best keratomes or pointed knives, no avulsion of Des- cemet's membrane is seen. As the tip ofthe keratome is advanced beyond the area of penetration, the sides of the keratome or knife now slice the adjacent tissues. Unless the knife blade is dull, the lip formed by the stretching of Descemet's membrane during this slicing is estimated to be less than 50,u wide during its formation. The elastic properties of Des- cemet's membrane are such that this lip immediately disappears or coils inward. The anterior edge of Descemet's membrane lies a fraction of a millimeter anterior to the internal margin of the stromal wound."6 Once an anterior flap of Descemet's membrane has been detached, it poses an additional hazard during the introduction of other instruments into the anterior chamber.17 Although structural analyses have shown Descemet's membrane to be of uniform composition,18 there must be a subtle inhomogeneity, since the membrane tends to coil.19 Ifthe wound is extended either with the edge ofthe keratome or with a knife, there is a greater danger ofstripping Descemet's membrane, which now lacks the support ofintraocular pressure. Stripping can be minimized by angulating the knife so that the tip advances before the haft, compres- sing Descemet's membrane against the overlying stroma as it is cut. This slicing of Descemet's membrane against a supporting body of stroma mimics the action of a corneal scissors. In a series of978 consecutive cases in which penetration was made with a keratome, stripping of Descemet's membrane was observed in only one case (Table II). In eight cases, however, the incision was abandoned when it was observed that the keratome tip was tenting Descemet's membrane rather than slicing cleanly through it. In contrast, in a recent series of 197 Wound Healing 429

TABLE II: STRIPPING OF DESCEMETS MEMBRANE* SUPERBLADE KERATOME (STORZ) (MEDICAL WORKSHOP) No. of cases 978 197 Aborted 8 0 Stri pin1 8pentZly 1 1 Laterally (0) 7 *The stripping reported in this table was observed at a postoperatively. None ofthese cases was observed at surgery; I have only seen one case at surgery in over 2,000 operations. Absence of lateral stripping by the keratome is noted in parentheses; no attempt was made to enarge the wound laterally with this instrument, since it was found unequal to the task years ago. The lateral stripping with the Superblade occurred at the left end ofthe wound where I have the most problem in control (being right-handed). The wound is now enlarged with a Superblade only in thLe central 5 mm of the wound where I have maximum control. Lateral enlargement is better done with scissors. consecutive cases in which the wound was enlarged with a Superblade after perforation had been made, 4% of the cases showed a small tag of Des- cemet's membrane in one area or another. Meticulous attention to keeping the tip ofthe blade ahead ofthe heel has reducedthis problem, but because ofthe difficulty ofkeeping both tip and haft ofthe knife blade in exactly the arc desired, I prefer to enlarge the wound with scissors. Although Scheie17 speculates on stripping caused by scissors, and Jaffe20 says it is more common with scissors-enlarged sections than with knife sections, Weve,21 Sugar,19 Samuels,22 and Scheie himself"7 all accuse dull keratomes or other knives as well as secondary stripping by spatulas (common in cyclodialysis) and irrigators. The stripping observed in my cases has been in the part ofthe section made by aknife or keratome, not by a scissors. While writing this thesis, I produced a major stripping of Descemet's membrane introducing a capsule forceps when my erysiphake failed.

SCISSORS WOUND FORMATION Because of their relative dullness, scissors blades produce much more crushing oftissue, and would not cut at all except that each blade supports the tissue being acted on by the other. The advantages ofscissors sections, therefore, are that they can be performed slowly and precisely; that the blades always cut into the tissue from without, avoiding stripping of Des- cemet's membrane; and tha-t iris snagging can be avoided since no sharp tip protrudes through the posterior surface ofthe cornea. On the other hand, there is increased endothelial trauma, and an inadvertent iridotomy occa- 430 Drews

TABLE III: CORNEAL SECTION WITH SCISSORS FULL THICKNESS AFTER DEEP GROOVE Ease of performance Difficult; need very sharp, Easy relatively stout scissors Ease of control Good, with good scissors Better Smoothness of cut edge Excellent Can be uneven when scis- sors blades do not enter at the base of groove Two-plane character Satisfactory Regulatable Healing Edema Blebs No difference Wound leak Gonioscopic appearance Early (2-8 wk postopera- tively) No differene - Late (6+ mo postoperatively) sionally occurs. The amount ofcrushing ofthe tissues can be kept to a minimum by using sharp scissors and by making a deep groove with a knife, cutting only the posterior layers of the cornea with the scissors. While a full-thickness scissors section does result in a two-plane incision, as Troutman23 has said, it does so because of the sliding of tissue between the crushing blades, which should be avoided. No adverse effects have been detected from full-thickness scissors sections, nor has poorer wound healing or any greater local corneal edema been seen. In a series of patients in which dissection was purposely made to one side first with deep groove and scissors and to the other with scissors alone, the differences between the two sides are tabulated as shown in Table III. The amount and direction of tissue sliding during the crushing by the scissors can be controlled grossly by the position ofthe two blades relative to each other. As Troutman has shown,23 if the external blade is central to the internal blade, the section tends to be more perpendicular. When the internal blade lies central to the external one, a more sloping, two-plane incision is made. The author's preference for groove and scissors sections is influenced by the track suture technique. It is easier to retrieve preplaced (track) sutures from agroove than to track across an open (full-thickness) wound. The latter can only be done with certainty if a blunt tracking needle is used; blunt needles swedged on silk sutures are not available. Three basic scissor blade shapes are available for corneal sectioning: (1) straight (angled), (2) curved in the plane of the instrument, and (3) curved out of the plane of the instrument (right- and left- hand models). The choice ofblade configuration will depend not only on the surgeon's Wound Healing 431 preference but also on the angle atwhich the scissors approaches the tissue. Right- and left- hand curved scissors must be held at right angles to the tissue. Their curvature shouldbe such thatthey followthe natural arcofthe limbus fairly closely, since adjustments with curved scissors while cutting are difficult (as anyone who has tried to make paper cutouts with fingernail scissors can attest). Scissors in which the blade curves away from the handle in the plane of the instrument can be used only when the plane of the instrument approaches the plane of the iris for an extremely beveled wound. The straight corneal scissors has the advantage ofallowing considerable control during cutting, and the disadvantage ofrequiring that control. It is best used with at least a moderate amount of beveling. It is unusual to be able to make the entire lengthening of the corneal section with a single scissors stroke. Nor is this usually wise: the entire length of the scissors blade is not likely to be in optimum position with respect to the limbus. Furthermore, experience shows that what was presumed to be acorrect position changes as the scissors blades are actually closed. For this reason, most scissors sections are made in multiple bites. Complete closure of the scissors blade after each bite makes a ragged section. An analysis ofthe events ofscissors sectioningwas made from three approaches: (1) from without, (2) using gonioscopy during surgery, and (3) from within Eye-Bank . As one blade tip passes the other, the tissues are forced apart to accommodate the thickness of the closed blades. This causes tearing or splitting especially of the internal part of the wound, which almost always occurs at an angle to the wound direction. A wound made without completely closing the scissors blade maintains the direction of the cut at the incompletely cut end. It is easy to advance the scissors in such a wound and to make another bite, which, because of the effects of tissue compression and sliding, becomes an almost perfect extension ofthe previous wound, providing only that the angle at which the scissors ap- proaches the tissue has not been changed. If the scissors has been closed completely and the tissue torn, it is often impossible to extend the wound in a continuous line from the previously smooth portion of the wound. In- stead, the scissors tend to slide into a slightly displaced position in one of the tears, and the resulting wound is scalloped or jagged, especially on its inner edge. Jose Barraquer23 designed scissors with stops to prevent complete clo- sure ofthe blades. The stop can be moved aside for the last stroke or for any other occasion as desired. Closure of scissor blades can also be prevented by allowing the side ofthe middle finger to enter partly between the handle shafts while it supports the scissors. 432 Drews Unequal blade lengths or sharp tips may be advantageous if the blades are fully closed at each stroke. A longer internal blade helps to keep the scissors from sliding out of position. Sharp tips, being thinner, tear less when the blades are fully closed, but sharp tips may wound the iris inadvertently. Scissors with a long, blunt lower blade and a sharp, shorter upper blade are an interesting compromise. I would rather not close the blades. The finished wound can be analyzed gonioscopically, observing three specific zones: (1) the zone of knife penetrance, (2) that portion of the wound made by slicing of the tissues with the knife blade, and (3) the scissors section. The late gonioscopic appearance of these three parts of a wound is tabulated in Table IV. A careful analysis ofthe wound gonioscop- ically has led to an analysis of some of the events leading to this final appearance.

IMMEDIATE (ELASTIC) CHANGES IN THE POSTERIOR CORNEAL WOUND As mentioned previously, the immediate appearance of the posterior corneal wound depends considerably upon whether this wound was made by an instrument coming through the corneal tissues, pushing stroma and Descemet's membrane in front of it, or by an instrument that was intro- duced into the anterior chamber and then cut outward, pressing Des- cemet's membrane and the inner layers ofthe stroma against other layers of cornea. When penetration is made from central tissue into the anterior chamber,

TABLE IV: GONIOSCOPIC ANALYSIS OF RESULTS OF DIFFERENT MEANS OF WOUND FORMATION ZONES APPEARANCE Central-knife or kera- Very smooth tome penetrance Lateral-knife slices Tags of Descemet's membrane occasionally seen Peripheral-scissors section Very smooth Inadvertent iridotomy was common before operating microscope and softening of the eye preoperatively became common All Beveling is surprisingly even in the three zones It is difficult to see a junction: the three zones look very similar gonio- scopically once healed, but the scissors portion has a slightly smoother surface Wound Healing 433 the resulting deformation, stretching, dehiscence, ripping, and slicing of tissues are followed immediately by an elastic recoil of Descemet's mem- brane and a pouting ofthe inner wound lip. The immediate pouting may be less if Descemet's membrane is detached, but this beneficial effect of the stripping of Descemet's membrane is temporary. In extremely small wounds, such as those made for needlings or peripheral iridectomy, elastic pouting prevents perfect apposition of the inner wound lip. Contrary to the study by Weene,24 in the author's experience even an extremely small wound can leak temporarily ifit is made perpendicular to the corneal surface. In an oblique stromal wound, which is not too many corneal thicknesses long, intraocular pressure will wedge the inner stromal leaf against the outer shelf and the stromal part of the wound can be self-sealing. But the elasticity of Descemet's membrane prevents apposi- tion of the inner wound margin to a degree dependent on the amount of local stromal support. This recoil is greatest if the overlying stroma is extremely thin (a very oblique wound) or absent (Descemet's membrane stripped). Since most corneal wounds are much larger than needle-knife or peripheral iridectomy wounds, and since intraocular surgery usually re- quires a quarter ofan hour or more, the immediate changes in the wound margin are oflittle consequence except as these are augmented by time and by abrasion ofthe inner wound lips by various instruments introduced into the eye. The vulnerability ofthe anterior wound lip to further stripping of Descemet's membrane is not so much a function of the wound configura- tion as it is a function ofthe direction in which instruments are introduced past the cornea. There is a greater tendency to strip Descemet's membrane with a reverse Pierce-Charleux incision, slanted toward the chamber an- gle, than with a standard incision beveled toward the . The reverse- beveled incision is a considerable hindrance ifmuch instrumentation is to be done within the anterior chamber.

DELAYED CHANGES Within minutes after a wound has been formed, the exposed stroma, no longer protected by the endothelial pump, begins swelling as it imbibes aqueous. This further increases the pouting of the inner wound lip and accounts for the ridge observed by Kirsch.25 This exaggerated pouting would make perfect apposition of the posterior wound lips exceedingly difficult even if techniques could be developed to allow visual control of their closure at the time of wound repair. Within a half hour after the wound has been made, leukocytes begin arriving in the wound margins from the tears.26'27 A few hours later they 434 Drews also invade from the limbal vessels.28'29 The volume of tissue in the pos- terior wound lips is increased, both by the direct increase the lymphocytes cause in tissue volume and by the edema that attends their presence, with further pouting. Some ofthe leukocytes enteringthe aqueous adhere to the endothelial cells of the cornea and interfere with the endothelial pump. Stromal edema from these souces can be improved by the judicious use of topical . Excessive corticosteroids are believed to delay wound healing. Clini- cally, perhaps "excessive" amounts of are those which pro- duce a completely quiet eye for a given patient. The amount of cortico- steroids used in most animal experiments has been overwhelming, making clinical extrapolation ofthe results speculative. Much ofthe human experi- ence reported is anecdotal and inferential. On the other hand, the bene- ficial effect ofinflammation on rapid, solid wound healing is well known. No specific analysis ofcorticosteroid use on anterior or midcorneal vs posterior wound lip effect has been published, but some inferences can be made from histopathologic experience.30'16 It is not uncommon for the posterior lip never to heal31'32 or for the posterior wound to fail to model itselfback to the preincision shape. Clinical experience with late formation ofexten- sive synechia in a few cases confirms Swan's thesis that exposed stromal surfaces may remain raw, unhealed, or capable of forming synechia for many months after surgery. Bleeding of the wound with filing of the separated tissues by glue-like clotted blood may seal the wound temporarily. Whether wound healing is impaired by the separation of the wound edges by the clot, or is hastened by its contracture and the irritation it incites, remains unanswered. Prob- ably both mechanisms occur so that clotted blood in a wound may be a mixed blessing, depending on whether the wound would gape without it.

ALTERATION OF WOUND SHAPE BY WOUND REPAIR Corneal wounds, as all others, tend to zipper shut, healing from end to end rather than across the gap. The greater pouting ofthe unsupported central portions ofthe wound may partly explain this effect. The healing pattern is purely dimensional in origin. A gap 20,u in width, such as is found at the ends of a wound, will close ten times as fast as a gap 200u in width at the center. Thus, the ends of the wound heal much more rapidly than the central parts, and the wound appears to close by zippering from the two ends. It is also true, ofcourse, that fibrocytes can invade the end ofa wound from three sides instead of two, but this again is a matter of geometry and not an abhorrence of the central part of the wound by the healing mecha- nism. Wound Healing 435 Healing ofthe central wound also proceeds from anterior to posterior31; the healing of the posterior wound is the most precarious. Kirsch's ridge can persist: out of 700 patients operated on for cataract, two show poor wound healingwith a ridgethat has persisted more than 18 months. In both cases, the ridge is accompanied by overlying corneal edema and, in my opinion, represents edema of the wound lips. Suturing ofthe outer layers of the wound may only make the inner lips pout more in the early postoperative course.' This is easy to demonstrate in the enucleated eye as a distinct buckle, observed from within as sutures are tightened. Even ifthe sutures are placed as deeply as two thirds through the cornea, the tighter they are tied, the greater the gaping ofthe internal wound lip. Perhaps this is one of the reasons why many avoided large numbers of heavy silk sutures in the past. A number ofsurgeons advocated four, three, or even two sutures as the optimum number to close a 1800 corneal section, arguing that additional sutures could compound the problems of wound alignment.31 But align- ment by sutures concerns only the tissues they embrace. Through-and-through nylon sutures immediately give rise to a concen- tric pair of grooves along the inner and outer edges of the corneal bites if tightened too much. These grooves reflect a compression of the wound in the area of the overtight suture and cause a marked increase in corneal curvature in the plane of the suture (Fig 3). It could be argued that buckling of the tissue even in the case of through-and-through sutures is caused by the reverse curvature of the limbal area as the curve of the cornea is ifileted into the curvature of the /*4 loose - +Xgood k .- tight

FIGURE 3 Tissue approximation and compression, reflecting effects seen in bank eye studies. Posterior "lambda" gape seen with sutures that are too superficial is exaggerated ifthese are tightened. Overtightened nylon sutures compress tissues, producing a groove at each end of the bite. More importantly, this distortion results in arching of the cornea with marked with-the-rule astigmatism. 436 Drews . But a similar double groove is seen around the edge ofa corneal graft if the sutures are overly tightened. The important alteration ofwound shape by deep sutures, ofany kind, is the better coaptation of the internal wound lips that these sutures can afford. They can also make such coaptation worse by forcing tissues into a distorted shape. For example, in a series of 80 patients, 28% (22) of such deep sutures showed malposition of the internal wound (Table V). Most commonly the needle had penetrated deeply but incompletely on the corneal side ofthe wound but was brought through the entire thickness of the cornea on the scleral side. Such a suture literally bound the internal wound lip into an abnormal configuration. Where the inner wound lips are properly approximated, however, there is a secondary wound "end" from which the zippering of the wound can occur in both directions toward the next suture. Well-approximated inter- nal wound lips heal much more rapidly and with faster resolution of the overlying stromal edema than those where the wound pouts. Unfortu- nately, the astigmatic error, rather than stabilizing earlier as might be hoped, continues to change over a period ofthree years or more in many of these eyes, giving clinical evidence oflate modeling ofthe wound in spite of optimal approximation. Most wounds revise their shape considerably in the weeks and months following surgery, remodeling toward the normal contour ofthe tissue. The pouting of the lips gradually subsides and the inner parts of the wound coapt. Histologically, Descemet's membrane may often not be re- formed,32 but this cannot be visualized at the slit lamp either by external or gonioscopic examination. The pouting inner lips disappear as distinct landmarks in most cases, and the mound of compressed tissue smooths over. The "lambda" configuration of the inner wound seen in some cases decreases with time (Table VI).

II. WOUNDING OF THE IRIS SURFACE

IRIS ANATOMY AND GENERAL CONSIDERATIONS The anterior surface of the iris is composed of fibroblasts,33 beautifully

TABLE V: LATE INTERNAL WOUND SURFACE: GONIOSCOPY (MICROSCOPIC) SUTURE CLOSURE GAPE MISALIGNMENT MOUND SMOOTH Silk 4/80 0/80 0/80 76/80 5% 0%i 0%/ 95% Nylon 0/80 22/80 53/80 5/80 0% 28% 66% 6% Wound Healing 437

TABLE VI: LAMBDA SHAPE* SUTURES 6 WK 6 MO 3YR Silk (and collagen) 44/300 18/276 2/187 15% 6.5% 1. 1% Nylon added 8/243 6/147 0/43 7.4% 4.1% *In at least 2 clock hours of the wound. illustrated in scanning electron micrographs in the recent article by Rod- rigues and colleagues.34 Perhaps it is not surprising that, given the least inflammatory stimulus, the iris forms abundant synechiae. If it can form synechia to the cornea, trabeculum, lens, and vitreous face, why not synechia to itself, and why, therefore, the dictum that iris wounds cannot heal? The failure of a cut iris edge to heal itself is well documented.7-9 35 It remains unchanged years later, with no smoothing and no migration ofthe anterior and posterior surface cells toward each other around the cut edge. The fibroblasts in corneal synechiae are said to be derived outside the iris.36 Despite this indisputable evidence, iris colobomas can be repaired by suturing, and although no scar results, the iris tissues unite.37 Emerick is said to have first reported this in 1957.38 Certainly the work by Macken- sen39 and Harms40 has been critically important in the acceptance of iris suturing techniques and the concept of the healing of iris wounds. The Symposium of the International Ophthalmic Microsurgery Study Group held in Lund, Sweden, in 1972 produced an in-depth discussion of this subject.5 It included formal papers by Rich and McPherson,41 Luntz et al,42 and Witmer and Remi.43 The current paper by Barner4 summarizes the literature well; other papers on iris healing are to be published soon. "Healing" of the iris is partly a matter of semantics. The union of cut iris surfaces occurs, but without fibrosis. Touch of the cut iris surface is not essential. A tissue bridge has been observed to form from two closely adjacent but nontouching cut iris sur- faces and, on contracture, has knit the two iris edges together again (Fig 4). Ehinger and Palm35 illustrate a "fine tissue bridge ... between the wound lips" ofa microscopic gap in an iris repair but conclude that there "was no sign ofactive repair" because this was not scar tissue. Harms45 has reported a case in which an iris wound healed and remained closed even though the nylon suture loosened or was never tight.

INADVERTENT VIOIATION BY SHARP INSTRUMENTS The surface ofthe iris can be wounded easily with-the incision knife while 438 Drews

FIGURE 4 Iris repair in 15-year-old who suffered fireworks injury at age 6. Iris coloboma was repaired with 10-0 nylon sutures, but closure of upper suture was not complete and was worrisome because oftension on it. Extensions oftissue appeared from edges ofiris and by six months had bridged narrow gap. Only minor contracture ofthis "scar" has occurred in three years, but it is holding well. A: One week after surgery. Note rounded tips ofincompletely closed iris pillars. B: Nine months after surgery. Note narrow tisue bridge. entering the anterior chamber. Such wounding is much more likely to occur if the anterior chamber collapses. Gonioscopic observation post- operatively shows that such wounds of the iris surface are likely to form synechia. Extension of a corneal wound using a knife with its tip in the anterior chamber poses an increased hazard to the iris. Ifthe tipofthe knife engages the iris stroma while being moved laterally to extend the wound, the surface of the iris will be wounded; the iris may be dragged along with the knife, resulting in an iridodialysis. Awkward manipulation of the scissors or knife to distort or press on the globe will generate a wound leak and relative vitreous pressure, pressing the iris into the instruments being used to extend the wound. In advancing a scissors blade under the cornea to extend a section, it is easy to inadver- tently wound the iris surface with the tipofthe scissors or to catch a knuckle of iris between the scissors blade and the cornea, making an unplanned iridotomy. Meticulous technique and careful observation of the surface of the iris under microscopic control can minimize such surface . However, minor iris injuries still occur in about 9% ofthe author's cataract patients, and in a larger percentage of those patients receiving corneal grafts.

IRIDOTOMY A radial peripheral iridotomy is less likely to form anterior synechia but is Wound Healing 439 more likely to be sealed by synechia to the vitreous. Most surgeons make the peripheral iridotomy concentric to the limbus so that it gapes well. Depending on how the iris is grasped, a concentric iridotomy tends to have the shape of an upside-down, broadened "V". The central flap ofthis "V" usually rides anteriorly, and was seen to be involved in a small wound synechia in up to 30% ofthe patients in whom this technique was used, in at least one of the two iridotomies made. In trying to avoid all synechia, I abandoned iridotomies about five years ago.

IRIDECITOMY The deposition of various types of foreign material by an iris forceps is seldom documented, but most occur rather frequently and would be an additional factor inciting iritis.4-48 An iridectomy has the immediate advan- tage that tissue traumatized or contaminated by the iris forceps is cut away. On the other hand, since there is greater stretching of iris tissue, and a much larger defect is produced in the iris, there is a much greater chance of hemorrhage, both from tearing ofthe iris base and from transection ofiris stromal vessels. One of the advantages of a radial peripheral iridotomy is the tendency to avoid such bleeding. The hole in an iris does not have to be large to be effective, as long as postoperative inflammation does not seal it against the vitreous face. The need for a peripheral iridectomy to be basal has been discounted long ago even in phakic eyes. That the iridectomy continues to be basal in many cases, and even larger than anticipated, is generally due to a lack of knowledge concerning the mechanics and technique of iridectomy. Large blades on the iridectomy scissors force the surgeon to lift the iris tissues forward, higher than the plane ofthe wound, for the scissors blades to reach the tissues. This places a strong pull on the iris base, not only by the forceps but also by the superior blade of the scissors, as it drags iris tissue toward the inferior blade as the blades close. Frame-by-frame analysis of motion picture films has disclosed a second important factor in controlling the shape and size of an iridectomy: the speed of closure of the scissors blades. Aqueous lies under the peak of tented iris. Rapid closure of the scissors blades traps a small droplet of aqueous in the pocket formed by the dome of iris being excised by the closing scissors blades. This droplet ofaqueous converts the tented iris into a small balloon, drawing more iris upward between the closing scissors blades than originally intended. The scissors blade edges do not meet simultaneously along their length in a clipping action but close sequen- 440 Drews tially, starting with the heel ofthe blades and advancing toward the points. Analysis shows that, as this approximation ofthe blade edges proceeds, the droplet of aqueous trapped under the iris anterior to the scissors blades rushes toward the tips, lifting more and more iris up into the advancing blade closure and resulting in an iridectomy that is much larger than expected and triangular in shape. If the scissors blades are closed slowly, or the closure is halted midway for an instant, the fluid trapped under the iris can drain out posteriorly or under the edges ofthe cut iris. There is no drawing forward ofadditional iris into the scissors blades, and the iridectomy size can be controlled pre- cisely. An iridectomy made slowly will be round and have extremely sharp edges. In discussion McCulloch49 pointed out that "a broad iridectomy will tend to have weak or flappy sides which may adhere to the corneal wound." Whereas synechia to the edge ofan ordinary iridectomy occurs in up to 30% of my aphakic patients, synechia formation to such a nonbasal, sharply formed small iridectomy occurs less than half as often in patients I have examined.

IRIDODIALYSIS When iridodialysis occurs during surgery, it is invariably secondary to iris traction. Traction ofthe iris centrally with a forceps is an obvious way to produce an iridodialysis. Now that a basal sector iridectomy is no longer a standard part of the surgical procedure, the production of an iridodialysis by the dragging forward of the iris around the corneal wound is less well ap- preciated. Traditionally, a sector iridectomy was best made by grasping the iris with forceps one third of the distance from the surgical limbus to the pupil. In so doing, the iris would be grasped about halfway between the iris root and the pupil. If the iris were now withdrawn from the wound far enough to present the pupil margin in the wound, the base ofthe iris would also be pulled free from the and into the wound as well. The iridodialysis produced obviously extended much farther to either side than the iridectomy. It was for this reason that some surgeons attempted to refine the procedure by cutting the iris radially from the pupil into the chamber angle and then tearing across the base. Without gonioscopic control, this maneuver carried the hazard of wounding the ciliary face. Occasionally iris may be caught and torn from its base by the instrument used to grasp the lens: erysiphake, forceps, or cryoprobe. If recognized early enough, the resultant iridodialysis may be limited by abandoning the surgical maneuver and reapplying the instrument without iris attachment. Wound Healing 441 The edges ofa limited iridodialysis almost invariably show synechia: 87% in cases recorded by the author. The combination ofraw, freely moveable iris and blood appears to guarantee synechia formation. Unfortunately, an iridodialysis may be painful, and the patient mayjerk his head as the dialysis begins, resulting in total avulsion of the iris. Synechiae form where remnants ofthe iris root remain. With a routine silk suture closure, these eyes tend to have much more corneal astigmatism, and their poor visual acuity is a result not only of poor imaging of the peripheral corneal rays but also of a greater central corneal astigmatism. Two patients followed up with surgical hadcentral corneal astigma- tic errors of 3 and 5 diopters, respectively, by manifest refraction. Keratometer cylinder measurements were greater and irregular. The ex- perience with total iridodialysis is too small for statistical significance, but in view of the other findings presented in this paper, these cases may be noteworthy.

BLUNT INJURY An inflammatory response in the iris can be stimulated simply by stroking

FIGURE 5 Depigmented circular crypts in iris appeared where Jervey iris forceps cups were applied to lift iris and support it for iridotomy. They seem permnanent, having remained unchanged for up to 17 years in patients underobservation. 442 Drews its surface.50'51 For this reason, manipulation or massage ofthe iris should be kept to a minimum during intraocular surgery. Tearingofthe iris surface stimulates even more reaction. If the iris surface is frayed, formation of peripheral anterior synechia occurs in two thirds of cases. Therefore, greater efforts should be made not to fray the iris surface. In corneal grafts where synechiae are particularly undesirable, a frayed area may even be converted into an iridectomy to avoid synechia to the graft wound. Little attention has been paid to crush injury ofthe anterior iris. Perhaps this is because the evidence is not usually dramatic enough to attract attention. Iris crushed between the cups of the Jervey iris forceps, how- ever, shows a distinctive double circle of anterior iris atrophy (Fig 5). Synechiae have not been seen in these areas.

III. EFFECTS OF THE OPEN CORNEAL WOUND

STROMAL EDEMA The imbibition of water by corneal stroma that has been shorn of its endothelial protection occurs rapidly enough to contribute to the Kirsch ridge.25 The rate at which fluid can seep into more distal parts ofthe cornea is balanced by the endothelial pump so that the edema and thickening are limited to an area immediately adjacent to the wound. As might be expected, the greatest stromal edema occurs around the wound in a patient who has poor corneal endothelium. One such patient, whose internal surgical wound appears not to have healed even after two years, has stromal edema extending visibly 3 mm into the upper parts ofthe cornea. Her central endothelial cell count is 746 cells/sq mm. Endothelial cell counts in the upper part of the cornea are not possible because of the edema. Minor defects in the posterior corneal wound can be effectively closed to aqueous, not only with endothelium but also with iris. Large defects and wound dehiscences with iris incarceration may leak around the iris,31 with the iris acting as a wick in an iridencleisis.

CHRONIC IRRITATION The cardinal signs of inflammation are reminders that the inflammatory response itself is accompanied by a further accumulation of fluids in the inflamed tissues, compounding the effects of aqueous imbibition. Local injection (rubor), tissue swelling (tumor), discomfort (dolor), and local tissue heat (calor) are all demonstrable in patients with posterior wound gape. The fifth cardinal sign (loss of function) is perhaps characterized by corneal loss of strength, contour, and transparency, the three basic func- Wound Healing 443 tional properties of the cornea. Aqueous differs significantly in its composition from interstitial fluids. Whether its irritant nature stems from this difference in composition or whether there are additional biotoxic complexes in the form ofprostaglan- dins or unknown factors is currently the subject ofconsiderable speculation and debate.52- The failure of setons to produce permanent filtration because offibrosis around them, the limitation in size ofifitering blebs, the clottingofblood in the anterior chamber, and the inflammatory response of the open posterior portions ofa corneal wound when exposed to aqueous are all examples ofits incompatibility with tissues other than endothelium. Perhaps failure of iris healing is another example, as Snell believes.10 Can the prolonged inflammation seen with vitreous incarceration be caused by the vitreous wick providing access of the aqueous to the corneal stroma? Vitreous adhesion can occur in eyes in which the posterior wound remains open when the vitreous face ruptures. In some cases, iris and vitreous incarceration occurs even without wound leak. What is less well recognized is the occurrence ofamild chronic irritation in eyes with an unhealed posterior corneal wound, even without iris or vitreous incarceration. The mild chronic leukocytic infiltration is not ap- preciable clinically; the reaction may be mild enough that there are no cells or flare in the aqueous, but there may be a mild ciliary flush, and these eyes are more prone to cystoid .

IRREGULAR ASTIGMATISM Lack ofintegrity ofthe corneal wound can cause significant weakening and wound slippage with flattening of the vertical meridian and against-the- rule astigmatism, requiring a correcting plus cylinder at axis 180. External grooving of the wound is only occasionally seen, though in some cases it may be alarming. The more critically the wound is studied, the more universal the finding of some internal wound incompetence. Local corneal swelling produces asymmetric changes in corneal shape and, by definition, an irregular astigmatism. Even though the central cornea may be clear, this irregular astigmatism leads to a reduction in visual acuity. The demonstration of irregular astigmatism with a keratoscope, keratometer, or ophthalmometer is easy and dramatic. Retrieval of the visual acuity can be obtainedwith a hard contact lens, but ifthe irregularity of the astigmatism is great enough, there may be difficulty in the fitting, adaptation, and wearing of a contact lens satisfactorily. Furthermore, the tolerance ofa hard contact lens in the presence ofperipheral corneal edema may be poor. If the lens is tolerated, the edematous peripheral cornea is subject to deep vascularization in time. 444 Drews CONJUNCTIVAL BLEBS Even the smallest bleb is a sign ofwound leak. These are much more likely to occur when there is gross posterior wound gaping, especially if the deeper parts ofcorneal sutures are exposed, and even more commonly, if the corneal sutures are placed so as to misalign and distort the tissues between them. Gonioscopy in patients with small blebs rarely demon- strates a fistula but frequently demonstrates an internal wound lip. Limbal blebs are almost always attended by at least local irregular astigmatism even if this does not extend into the central cornea.

FLAT CHAMBER Loss ofthe anterior chamber threatens the integrity ofthe eye. Iris incar- ceration into the area ofwound dehiscence, with or without prolapse, is a fundamental ocular defense mechanism. The role of the iris in the healing of the dehisced corneal wound is of paramount importance. The revulsiveness of an iris prolapse or ofa mark- edly updrawn pupil may make the surgeon forget that the prolapse saved the eye. The iris prolapse is decried, rather than the wound dehiscence which has been blessed with a sealing knuckle of this ocular omentum.

IMPROPER REPAIR Almost by definition, the repair ofthe gaping posterior wound consists ofa knitting together of the stromal layers with fibrocytes, a bridging of the remaining defect by corneal endothelium, and, properly, the laying down by this endothelium ofa layer ofDescemet's membrane beneath it.30 After modeling, the final scar may be difficult to detect in histologic sections, although it is always readily apparent at the slit lamp or with gonioprism because of its loss oftransparency. Some wounds do not heal, and a swol- len edematous stroma unprotected by Descemet's membrane or en- dothelium persists. Wounds in which the iris does not assume a role in the repair may emphasize the reparative process by exaggeration ofthe prob- lems of proper healing. 1'32 Epithelial downgrowth5 is an exaggeration ofa normal reparative proc- ess.556,57 The external groove of the wound is normally invaded by epi- thelium, which is then pushed back to the surface as the stroma ifils in the defect. Verhoeff showed epithelial proliferation along a suture in 1901; others have confirmed this source ofinvasion.31 When something such as a wick of vitreous prevents stromal coaptation, it is not surprising that the epithelium may grow through the wound and spread in wrong directions as the epithelial edges seek out each other. Epithelium normally spreads until it finds more epithelium. Wound Healing AA45

TABLE VII: EPITHELIUM OBSERVED IN THE ANTERIOR CHAMBER AT SURGERY WITHOUT INTRAOCULAR LENS WITH INTRAOCULAR LENS Isolated epithelial plaques 23/100 8/400 23% 2% Epithelial tags extending through 5/100 10/400 wound 5% 3% Epithelium dragged in by iris 1/15 12/300 suture knot .. 4% Epithelial downgrowth 2/2,000 1/400

Epithelial downgrowth is most often found in eyes that have suffered complications at surgery, especially vitreous loss. There is usually a history of a stormy postoperative course-an eye that never quieted down and never achieved good vision.5`f The term "epithelial downgrowth" implies an invasion of the eye by epithelium from without rather than the spreading of implanted tissue. Epithelial cysts are accepted as growing from epithelial rests or im- plants.3'6163 It has been shown, unfortunately, that the cysts can convert into epithelial downgrowths if they rupture during removal.6" That being the case, it is likely that a "downgrowth" could occur from an epithelial rest in the first place. In cases where no conjunctival flap is made, careful observation as well as a cine analysis ofsurgery has occasionally shown the incarceration of a tongue of in the wound. Even more com- monly, a small plaque of conjunctival epithelium must be retrieved from the anterior chamber (Table VII). Some lens implants are sutured. The knot is usually formed outside of the eye and then tightened, sliding it through the wound down to the implant. In 12 ofthe author's first 300 Medallion lens cases, a small piece of epithelium was carried into the eye with the nylon knot. It is almost impossible to remove this epithelial remnant: it is tightly welded to the suture by electrostatic attraction and is often enmeshed in the knot. This isolated bit ofepithelium has not caused a problem, although it may persist for months. Problems in the repair of Bowman's membrane are unusual and do not influence the internal wound. Any wound that perforates Bowman's mem- brane will leave a scar. It is occasionally possible for stroma to overgrow in the process ofcorneal wound repair.2'65 '" Retrocorneal membranes and fibrous ingrowths may mimic epithelial downgrowth but are often self-limited. While imposing marked visual loss and major problems in surgical reconstruction of the anterior segment, fibrous ingrowth may not destroy the eye in adults. In children, fibrous ingrowth is more common and more devastating.67 446 Drews Wishful thinking may lead the surgeon to miss the diagnosis in a child whose recurrent pupillary membrane is continuous, through the iridec- tomy, with a broad limbal scar. This occurred in a child on whom lens implantation was performed. The lens is now incased in fibrous tissue. The case in Fig 3 in Hiles' series of children has a typical history and results, although not recognized by him either at surgery or when the paper was written.68 He has subsequently made the diagnosis (oral communication, May, 1976). Duplication of Descemet's membrane is not an active process since Descemet's membrane does not repair itself. It stands, rather, as a hallmark of recurrent breakdown ofthe inner corneal surface.69 It is most commonly encountered by the surgeon in cases of luetic interstitial . That it is rare in wound repair attests to the unidirectionality of the wound repair process. The formation ofDescemet's membrane tubes70 gives a curious proofof endothelial proliferation. Endothelium, like epithelium, normally spreads until it meets itself. The obvious exception in the eye is at Schwalbe's line. Given the opportunity to vault this barrier, endothelial "downgrowth" can also occurwith liningofthe iris or vitreous face with corneal endothelium.71 IV. SYNECHIA FORMATION TOUCH AND GLUE Synechiae can occur in the absence of a wound. Examples include the peripheral anterior synechiae seen in chronic angle-closure , chronic iritis, and (away or separated from the wound in) persistent flat anterior chambers after cataract surgery or filtering operations. All that the fibroblasts composing the anterior iris stroma appear to need in order to form synechia is approximation ofthe tissues and the stimulus and "glue" of inflammation. Absence ofeither ofthese factors makes synechia formation without a wound unlikely. Synechia formation is remarkably enhanced when there is an iris or corneal wound. When both surfaces are wounded, synechia formation almost becomes the rule. It is unusual not to see synechia at least at one edge of an iridectomy. It is almost as though a gaping internal corneal wound and the raw surface ofthe iris were drawn to each other. Any degree of fraying or wounding of the iris surface, iridotomy, iridectomy, or iridodialysis almost guarantees synechia formation ifthe raw edges are in a position to touch an unhealed wound surface. One wonders ifthe intermit- tent touch that may be afforded by iridodonesis is not sufficient in some cases. The incidence of synechiae around sector and peripheral iridec- tomies and iridotomies is hopefully much more common than the incidence Wound Healing 447 of wound leak sufficient to draw the iris into the fistula. Perhaps, on the other hand, the unexplained synechiae are mostly a matter of inadequate observation or investigation of the integrity of the wound. Certain (patho)physiologic glues can greatly augment the process.31 The glue-like properties of clotted blood in the anterior chamber are omitted from most discussions ofanterior chamber hemorrhage. The tenacity with which clots attach themselves to the iris can make their removal difficult during surgery. A clot of blood that appears in the upper chamber angle during the postplacing of sutures can prevent centration of the pupil. Inflammatory exudates also apparently provide physiologic glues. Useful in wound healing itself, this normal body defense mechanism helps to

FIGURE 6 Elliptic distortion ofpupil in placement ofChoyce lens implant is common. This patient had a round pupil that gradually developed elliptic distortion as peripheral anterior synechiae formed at each end ofthe lens, between feet. AAR Drews explain the great augmentation ofsynechia formation in the inflamed eye. Late peripheral synechiae can occur in the crotch between the feet of Choyce intraocular lenses. This is a most peculiar area for synechia to occur. Presumably the irritation ofiris rubbing against this area ofthe lens is sufficient to set up enough local inflammation to induce synechia forma- tion. A round pupil following perfect Choyce lens insertion may be seen to become progressively oval and the iris drawn further and further toward the synechia. The synechiae occur both on the side ofthe lens that is against the insertion wound and on the opposite side where there was no wound. I do not have a significant experience in implantation ofChoyce lenses, but have seen this situation in patients referred in consultation. Ellingson has shown me photographs ofpatients with round for some months after surgery, followed by progressive distortion of the pupil toward the crotch in both directions as peripheral anterior synechiae form there (Fig 6).

SCAFFOLDS Even without direct iris-corneal touch, synechiae sometimes form. All that is required is a contracting scaffold. Clotted blood, organizing exudates, lens capsule, zonule, and vitreous, or a tag ofcorneal stroma or conjunctiva can serve to introduce iris to a posterior wound that is seeking fibrocytes for repair. A tiny iris synechia can also form an excellent scaffold for additional iris to climb into the wound. It is not uncommon to see zippering of synechia across a wound as a form of wound repair.32 It is extremely doubtful that most synechiae that extend more than 2 clock hours form in a single instance throughout this distance. Some zippering undoubtedly occurs in all synechia formation.

RESULTS OF SYNECHIA FORMATION The deleterious effects of synechia formation are well ingrained in our thinking. Ifextensive enough, the compromise ofthe trabecular meshwork can lower facility ofoutflow and produce secondary glaucoma. Updrawing ofthe pupil is common. The anterior displacement ofthe iris plane, which also accompanies an extensive synechia, is neglected in most discussions. When produced by a synechia that is well in front ofthe chamber angle- common in surgical wounds-the drawing forward of the iris to the synechia can promote goniosynechiae behind and beyond the synechia to the wound, especially if there is inflammation. In pupil-supported in- traocular lenses, displacement ofeither the pupil or the iris plane will carry the lens and its haptics toward the corneal endothelium. Even intermittent endothelial touch is accompanied by local , ciliary flush, and cystoid macular edema. Correction of the implant position in these Wound Healing 449 cases can be exceedingly difficult. Peripheral anterior synechiae also provide an immediate and broad source or reparative tissue to the gaping posterior surgical wound. They plug fistulas and obviate the need for corneal endothelium to dehydrate the stroma. They can prevent loss of the anterior chamber and invasion by bacteria or epithelium. Without discounting the significance ofthe astigmatic errors that accom- pany wound dehiscence with iris incarceration or prolapse, a study on my patients yielded surprising data correlating lack of iris synechia with a greatly increased average postoperative astigmatism. Averaging astigmatic errors in a series of postoperative cataract patients yields a standard deviation that, although clinically significant, needs further analysis. There are five configurations, which demand separate consideration (Table VIII): 1. The wound that heals well without distortion, without gaping, and without iris incarceration. 2. The wound that heals well, but with the aid ofreinforcing peripheral anterior synechia. 3. The wound with slippage or internal gaping deprived ofthe benefit of iris incarceration or synechia. 4. The dehisced wound, heralded by iris incarceration or prolapse. 5. The compressed, buckled wound produced by overtightened elastic monofilament sutures. Wounds 1 and 2 tend to have low astigmatic errors, rarely over 3 D and commonly less than 1 D. Wounds 3 and 4 are associated with wound slippage and high against-the-rule (plus at 180, or flat meridian at 90) astigmatic errors. This overwhelming shift of astigmatic error with a ten- dency for large against-the-rule problems is found in several series oflens implants72 and is one reason for the adoption ofmonofilament nylon sutures by a high percentage of lens implant surgeons. The type 5 wound configuration has a high with-the-rule (plus at 90, or

TABLE VIII: WOUNDS, SYNECHIA, AND ASTIGMATISM NO. OF CASES AVERAGE STANDARD WOUND TYPE PAS ANALYZED ASTIGMATISM DEVIATION (1 Solid -- 95 +0.75x 180 ±0.75x 180 Reinforced + to +++ 37 +0.75x180 ±1.00X180 (3) Gaped or slipped - 60 +3.00X 180 ±1.25X 180 (with IOL) (4) )ehisced ++++2 +4.00 oblique ... irregular (5) Buckled with + 50 +5.00X90 ±1.25X90 nylon sutures 450 Drews steep at 90) astigmatic error. This wound can often be converted to a type 1 or type 2 wound withjudicious cutting ofthe overly tightened sutures. The problem is when to cut them. If they are cut too early, the wound relaxes into a type 3 configuration either immediately or in the ensuing months or years. If they are cut too late, much of the astigmatic error may remain permanently. Unfortunately, wound healing is an individual process, and its predic- tions are subject to errors and disappointments. Wounds that are denied the access of iris have a much greater tendency to slip if closure is not

9 9 A8i3.12 t9-blL ~~~~~~~~~~36

8-\ /4

75 mICCA ts s : ECCE 6 ACLI FIGURE 7 Location and extent ofgoniosynechiae following cataract surgery. All patients had 1700 to 1800 incision above with similar wound closure. Solid and dotted bands denote synechiae in patients who had intracapsular (ICCA) and extracapsular (ECCE) surgery without lens implantation. The striped bands mark synechiae seen after intracapsular surgery with lens implants (ACLI). Wound Healing 451

TABLE IX: GONIOSCOPY OF CATARACT WOUNDS IN 79 PATIENTS NO. OF WITH PAS SYNECHIAE NO. (%) Without IOL ICCE 58 22 (37.9) ECCE 7 3 (42.9) Total 65 25 (38.5) With IOL ICCE 50 5 (10.0) Total 115 eyes perfect and healing advantageous.

GONIOSCOPY Lowe independently performed gonioscopy on 79 of my patients at least three months after surgery (Personal communication, 1978). A total of 115 operated eyes were examined. Patients were selected only on the basis of their random return to the office for postoperative follow-up care. A few patients were excluded because ofcorneal dystrophy. Special attention was paid to pigment in the chamber angle, and peripheral anterior synechiae were carefully mapped. Interesting cases were reviewed, but in no case were the findings ofthe independent examiner overruled (Table IX, Fig 7). Medallion lens implants were used in 114 of the 115 eyes. Wound closure and postoperative medications in the eyes with lens implants and in the control eyes were identical. In the 65 eyes without lens implantation, peripheral anterior synechiae occurred in 38% (25) of the eyes. These were extensive, involving more than 2 clock hours in half ofthese eyes. None ofthese eyes had secondary glaucoma, but that is a matter of chance. The presence ofan intraocular lens in the eye appeared to stabilize the iris plane and to prevent iris wound adhesion. The incidence ofperipheral anterior synechiae in the patients examined with intraocular lenses is only 10%. Certainly lens implantation does not decrease the incidence ofposterior wound lip problems or of wound leak. It should increase the amount of postoperative iritis. There is less motion ofthe iris itselfin these patients. There is a marked decrease in the access of vitreous to the anterior chamber: the implant tends to act as the "cork in the bottle," keeping vitreous behind the iris plane and preserving an intact or semi-intact vitreous face. Pseudophakodonesis and iridodonesis are present, but there must be enough stabilizing influence on the peripheral iris by the presence 452 Drews ofthe lens implant in the pupil to markedly decrease the incidence of iris wound touch, at least in this series of Medallion sutured lenses. The decrease in both percent and extent of peripheral anterior synechiae is striking. Major problems in wound healing are unusual now, and this series did not happen to include patients with dehiscence.

V. PREVENTION OF PERIPHERAL ANTERIOR SYNECHIA

ANTERIOR ENTRY OF THE INTERNAL CORNEAL WOUND Access ofthe peripheral iris to the corneal wound is a matter ofthe distance separatingthe two. Synechia formation requires eithercontact ora scaffold- ing. Both are much less likely over greater distances. Accordingly, the incidence of peripheral anterior synechia can be reduced by moving the internal opening of the corneal wound centrally away from the iris, by minimizing pouting of the wound lips, and by avoiding tags of stroma or Descemet's membrane that may hang posteriorly. A two-plane, groove-and-scissors incision is more likely to produce a broad shelfthan a single-plane entry or the two-plane profile achieved with scissors. The broad corneal shelf has many technical disadvantages; its chief recommendations are its tendency to a self-sealing posterior wound and a decreased incidence ofgoniosynechia. A wound which bevels sharply forward, entering the anterior chamber well into clear cornea, is more easily kept free of iris than the reversed incision of Pierce and Charleux, which shelves peripherally into the chamber angle.

PROPER WOUND CLOSURE The best wound closure before the widespread use ofthe operating micro- scope (and perhaps even since) was obtained with a variety of preplaced suture techniques. These were basically variants of either the McLean suture, preplaced across a groove, or the track suture ofVerhoeff, placed in effect before any wound had been made. Few surgeons execute these in nylon, andwith lens implantation, the use ofsilk or digestible sutures alone allows too much wound slippage. Suturing across a groove must be done with the needle entering the peripheral cornea exactly opposite its exit from the central cornea. The tendency is to enter the peripheral side of the wound more superficially and more toward the 12 o'clock position. Postplaced suturing has become more accurate with the increased precision ofwound closure provided by thc operating microscope. Optimum wound closure requires microsurgical control. Wound Healing 453 Most ophthalmic surgeons continue to think of closure of the limbal wound as though this were a single layer. It has been well known that a wound sutured too superficially would not be secure. Posterior wound gape has also been observed; besides, superficial sutures tend to slough early. The dicta to place sutures at one-half31 to two-thirds depth73 74 arose from concern about possible fistulization and epithelial ingrowth. Without current microsurgical equipment and needles, precise closure ofall layers of a limbal wound was not feasible. Deeper suturing with silk was, and still is, believed to be dangerous. The extremely deep suture may enter the anterior chamber either directly or within an area ofposterior wound gape. Especially with silk, such a suture could act as a wick, creating a fistula with bleb formation at best and increasing the risk of and epithelial downgrowth at worst.31 With nylon, this risk is believed to be minimal.75 Both the internal and external parts of the nylon suture quickly cut into the tissue and become buried. My usual cataract incision is about 1700, closed with three track silk sutures. Two collagen sutures are added, one beyond each of the lateral silks, and two figure 8 nylon sutures are placed between the silks. The first bite ofthe nylon is made at halfdepth, to bury the knot at this level. The second bite is placed as close as possible to Descemet's mem- brane, preferably through and through rather than too superficially. Gonioscopy postoperatively (Table X) shows that the sutures were placed through and through in 82% ofthe last 40 eyes (80 sutures), proofthat the effort at very deep placement is successful. This figure has remained fairly stable (70%Yo to 85%) for the last four years. About 50% of these remain exposed in the anterior chamber, or at least they bulge internal to Des- cemet's membrane. Perhaps there is a single layer of endothelium over them. Fistulas have not been a problem. Problems with the silk track suture position have been suspected for some time. Prejudiced toward posterior wound closure, sutures have been placed deeper. With this, small hemorrhages have been noted from the upper chamber angle after placement of the track sutures, while making the groove, before opening the eye. In all but two cases however, the sutures were found to be of proper depth in the groove. Occasional cases have shown a leak ofaqueous around one ofthe track sutures immediately after the placement, but all ofthese again showed proper suture depthwith no perforation when the groove was made down onto them. I believed I had perhaps opened a large aqueous vein since no other evidence ofentry into the anterior chamber was seen. The track technique uses a double suture-one 8-0 silk and one 6-0 454 Drews nylon-swedged onto a single needle. The nylon is removed after the groove is made, then the silk is looped aside and the eye is opened. Recently a silk suture loop appeared in the anterior chamber as its nylon mate was removed. The uncertainties about the hemorrhages in unopened angles and aqueous leak disappeared as the mental block against perfora- tion by the suture was removed. Gonioscopy both on the operating table and early postoperatively confirmed that the anterior chamber was entered with the needle, peripheral to the wound area. A large number of inadvertently perforating silk sutures, then have caused no harm. A series ofcases now gonioscoped before suture removal has shown at least one perforating silk suture in two-thirds of the eyes (Table X), an estimated 1,000 such sutures in the last five years. Even ifthis estimate is grossly in error, the number of patients at risk remains large. The techniques are being altered at once, but perhaps this is not the tragedy that had been envisioned.76 Silk sutures are routinely removed after one month (for the last 11 years). By then they are usually loose and easy to cut. On rare occasions in the past a small stream ofaqueous was recognized on removal ofa suture. Careful study ofthis series has shown an aquesous leak (Seidel's positive when no gross flow seen) in six ofthe 40 patients. This has subsided in a few minutes. Enucleated eyes were studied for the anatomy and mechanism of the problem (Fig 8). The suture passed through the cornea at two-thirds depth in the area where the groove intercepted it. But this was not the needle arc's apogee, and the needle continued into the chamber in the angle. In some instances, a deep chamber vessel apparently was wounded in the exit, causing the observed at surgery.

RETROSPECTIVE GONIOSCOPY An analysis ofthe gonioscopic appearance ofthe internal surface ofthe late wound has been disappointing. The areas ofcollagen and silk suture closure show either a smooth surface or a persistent lambda-shaped gape. The perforating nylon closure areas show either a persistent elevation of the tissues or a permanent misalignment of the internal layers, not seen with silk (Table V). Although the gaping wounds that sometimes occur with silk are intolerable, those wounds that did heal properly look much better than the nylon-closed surfaces. Although the defects are microscopic, perfect internal wound closure has not been achieved with nylon. Wounds closed with nylon and silk show much less final astigmatism in patients receiving intraocular lenses than wounds closed with silk alone however. Optimum closure ofthe internal wound margin is a paramount, ifincom- Wound Healing 455 pletely achievable, goal for the prevention ofperipheral anterior synechia.

INTACT IRIS SURFACE Maneuvers to avoid iris contact are not new. Stroking ofthe iris surface is enough to provoke irritation ofthe iris with constriction ofthe pupil and an inflammatory response.51 Eight percent of the patients with sutured Medallion intraocular lenses show a few persistent, thin, greyish or brown- ish precipitates on the posterior surface of the lens near the upper pupil border where the suture causes the lens to hug the iris and rub against it during motion of the pupil. The iris should be touched minimally during surgery and preferably with extremely smooth-surfaced instruments. Incisions in the iris can be made smoothly only with scissors: these

FIGURE 8 Findings of bank-eye analysis with deep placement of corneolimbal sutures. Needle has crossed area of future groove at optimum, deep level but continues posteriorly, entering anterior chamber deep in angle before arcing back out of sclera. 456 Drews

TABLE X: DEEP LIMBAL SUTURES 40 CASES DONE ANALYSIS OF LAST 40 CASES ONE YEAR AGO AQUEOUS SUTURE UN- PERFORATES LEAK ON BURIED IN- FISTULA (GONIOSCOPY) REMOVAL BLEB TERNALLY OR BLEB Track silk (3) In groove 0% Behind groove One or more 68% 15% 3% (1 case) Three sutures 0% Nylon, postplaced (two figure 8) One or more 82% 3% (1 case) 38% 0% should be ofthe highest quality and small enough so that the iris plane does not have to be elevated excessively. Multiple bites result in jagged edges and should be avoided. Maintenance of a deep anterior chamber during wound formation prevents inadvertent wounding ofthe iris by the knife or scissors. Iris forceps with teeth or cups should only grasp tissue that will be excised. Otherwise, smooth-tipped forceps are preferable, but microscopic control of their use is required. The iris should be grasped in the fewest places commensurate with atraumatic accomplishment of the maneuvers needed. Atraumatic placement ofa broad iris suture bite requires support of the iris with smooth forceps at both the entry and the exit sites, but no more. Where there is excessive iris trauma, increased postoperative iritis is found. Wounding ofthe iris surface invites broad local PAS. Minimal PAS are found around a nonbasal iridectomy, more around a basal iridectomy, still more with iridotomies (especially ifthey are inadvertent), and univer- sally with sector iridectomies (Table XI).

WOUND TOILETTE Prevention of peripheral anterior synechia requires avoiding or removing the scaffolds upon which synechiae can be built. Wound toilette is a term no longer used, but a concept as important as ever. It has a different meaning now than when iris, lens capsule, and large amount of cortex could be found in the wound after an extracapsular delivery. Meticulous microscopic inspection of the wound before leaving the field is still essen- tial. Even when the wound looks clean, distortion of the pupil must be considered a signal of wound inclusion. The Barraquer spatula can sweep the closed wound clean from within, clearing iris strands, a zonular fibril, or Wound Healing 457

TABLE XI: PERIPHERAL ANTERIOR SYNECHIA IN RELATION TO SURGICAL IRIS WOUNDS IN CASES WITHOUT LENS IMPLANT PERIPHERAL ANTERIOR SYNECHIA Iridectomy Sector 28/30 = 93% Basal 15/27= 56% Peripheral 6/80 = 8% Iridotomy Planned 15/48 = 31% Inadvertent 12/16 = 75% a remnant of capsule. A small strand of conjunctiva or corneal stroma inadvertently frayed in making the groove should be removed with smooth forceps. It is disconcerting how often one or another ofthese things occurs (Table XII) and to realize that many of them were not seen when the operating microscope was not used routinely.

INTACT VITREOUS FACE Prevention ofvitreous in the wound is best achieved by an intact vitreous face or by an intact posterior lens capsule. Of all the prerequisites and maneuvers, a soft eye is the most important in preventing vitreous loss. Meticulous anterior vitrectomy salvages most eyes in which vitreous loss occurs, with good visual results, but internal wound toilettement with a Barraquer spatula sweep after constricting the pupil remains an essential step. Unfortunately, vitreous can attach itself to a gaping wound even weeks after surgery, leading to late peripheral anterior synechia formation. A barrier in the pupil prevents this. Lens implantation can provide this barrier; an intact posterior lens capsule is physiologic.

TABLE XII: WOUND TOILEYTE (OTHER THAN VITREOUS LOSS) INCLUSIONS INCIDENCE Conjunctiva (no flap) 6/100 = 6% Comeal stroma 3/100 = 3% Iris 0/500= 0%* Lens capsule After rupture 1/30 = 3% Planned extracapsular 0/16 = f Zonule 2/1000 = 0.2% *Zero only because iris inclusions were cleared before closure was finished. fAuthor's experience is too limited. 458 Drews

HEMORRHAGE Clots in the chamber angle promote synechia formation. The contracting clot draws the iris closer to the cornea, irritates the iris, incites iritis, and can provide a scaffold for fibroblasts. Patient history should include patient bruising or bleeding, familial bleeding, and current therapy with blood thinners. Preoperative analysis ofbleeding tendencies and prophylactic use ofvitamin K where applicable can reduce hemorrhage during surgery. Conjugated estrogen (Premarin) was used briefly in the 1950s when it was supposed to prevent postoperative hyphemas. Double-blind studies discredited these impressions, and it fell from use. As usual, however, there was a grain of truth: I have found Premarin effective both in preventing and in stopping small vessel bleeding during surgery. A series of patients was chosen in whom cataract surgery was performed on both eyes, two days apart. When severe bleeding occurred during surgery on the first eye, the patient received an intramuscular injection of 25 mg Premarin preoperatively for the second eye. There was a dramatic reduc- tion in the amount ofbleeding in the second eye in all but two cases (Table XIII). A series with random alternate use has not been attempted: most patients do not need Premarin and, unless some means were found to predict those who do, the results of Premarin effectiveness would be indecisive. Hemorrhage during surgery can also often be dramatically improved by intramuscular or intravenous injection of Premarin. Routine oral prophylactic Premarin does not alter the incidence of postoperative hyphema, but does appear to improve excessive acute small vessel hemorrhage. Cautery can be extremely effective if controlled. Direct current cauteries are best used with the field wet by a thin layer of saline. A thin fluid film can prevent charring and tissue shrinkage without cooling the cautery excessively. It is almost impossible to achieve reproducible results, however. Pierce has an experimental unit that produces an exact tempera- ture even under a wet field (Personal communication, 1978). Until equally good units are available, a wet-field bipolar cautery is essential for fully controlled microsurgery.

TABLE XIII: BLEEDING DURING SURGERY PREMARIN PREOPERATIVELY FIRST EYE SECOND EYE (TWO DAYS LATER) Bleeding 3+ to 4+ 0 1+ 2+ 3+ to 4+ No. of eyes 23 0 16 5 2 Wound Healing 459 hemorrhages within the eye, eg, iris hemorrhage. Irrigation does not promote clotting unless intraocular pressure can be elevated considerably. Tamponade is most effectively obtained with a large air bubble. Others prefer this also.78 Ifthe anterior chamber is ifiled with air, the bubble also limits the spread of the blood to a small ring near the base of the iris. Large clots in the anterior chamber extending to the angle, especially beneath the wound, should be removed. They are best peeled off the surface of the iris gently with an olive-tipped cannula while irrigating. Often the entire clot cannot be removed gently. I have regretted leaving clotted blood in the superior chamber angle before implanting intraocular lenses. The updrawn pupil often persists. Vigorous attempts at correction after lens implantation has led to further bleeding.

INFLAMMATION Prevention ofinflammation is mostly a matter ofminimizing tissue trauma. Atraumatic technique can be markedly improved by routinely ifiming or taping all of one's surgery and critically analyzing each case. Inflammation can also be incited by irrigation, especially with un- physiologic or contaminated fluids, and by the introduction oftoxic foreign bodies. The introduction ofas few chemicals into the eye as possible, and a clean technique to avoid foreign material in the field, prevent cases oftoxic postoperative responses. The uninflamed eye may not heal as rapidly or as well as the inflamed eye, but it is also much less prone to synechia formation. I use rather small amounts ofcorticosteroids routinely (Maxitrol ointment, bid), but I do not hesitate to use and heavy topical corticosteroids when needed. Subconjunctival and systemic corticosteroids are also usedwhen required.

STABLE IRIS PLANE The iris must reach the cornea to form synechia. Ifthe wound geometry is favorable and scaffolds have been eliminated, the one remaining factor is stabilization of the iris plane. Theoretically this is enhanced by extracapsular surgery. Most large series obviate comparison with intracapsular results by employing much smaller wounds. Hoffer, however, has spoken ofa 20%o incidence ofminor peripheral anterior synechiae after phacoemulsification (Personal com- munication, April, 1978). The other singularly effective means of stabilizing the iris plane is implantation of a light iris-clip lens. Theoretically, chamber angle- supported, iris plane, and especially posterior chamber (after extracapsular surgery) lenses should also have beneficial effects, even though experience 460 Drews

TABLE XIV: PREVENTION OF PERIPHERAL ANTERIOR SYNECHIA 1. Moving the internal corneal wound centrally 2. Proper wound closure with a. microsurgical control b. deep appositional sutures, closing the internal wound 3. Avoiding iris trauma and controlling iris incisions 4. Meticulous wound toilette 5. An intact vitreous fice 6. Prevention and control of hemorrhage 7. Prevention and control of inflammation 8. Stabilization of the iris plane by a. (extracapsular surgery?) b. lens implantation with them is limited (Table XIV).

VI. CONSEQUENCES OF ANTERIOR SYNECHIA FORMATION BENEFITS OF PREVENTION Prevention of peripheral anterior synechiae allows the iris plane to main- tain its normal position and the pupil to remain round and central. The position of the iris plane is important in preventing zippering by progres- sive peripheral anterior synechiae. The position ofthe pupil is increasingly important as more and more patients are fitted with a contact lens post- operatively or with an intraocular lens at the time of surgery. The aphakic contact lens tends to ride low on the cornea because of its weight. Aphakic peripheral anterior synechiae occur mostly in the upper half of the eye, displacing the pupil superiorly and making an adequate correction with the contact lens more difficult. Displacement ofan iris-clip intraocular lens by an eccentric pupil greatly increases the risk of late complications. Corneal touch, even if intermit- tent, eventually leads to the triad of local corneal dystrophy, chronic iridocyclitis, and cystoid macular edema. Left undetected or unattended, the corneal dystrophy becomes generalized and the cystoid macular edema permanent. Prevention of peripheral anterior synechia is desirable for patients who are to be fitted with a contact lens, and is essential in lens implantation.

BENEFITS OF SYNECHIAE The prevention of peripheral anterior synechiae also prohibits the bene- ficial effects of iris inclusion in an inadequately closed posterior corneal wound. Inadequate healing of the posterior corneal wound is the single event most closely correlated with the higher degrees of against-the-rule astigmatism seen in lens implant patients as a group. The prevention of posterior synechiae in these patients delays wound healing and allows wound slippage with flattening of the vertical meridian of the cornea. Wound Healing 461 Patients with higher degrees of astigmatism (6 D or more by keratometry) usually have poor central visual acuity, partly because the astigmatism is not regular, and partly because of increased edema ofthe superior part of the cornea, encroaching on the pupillary zone. The iris plays a significant role in the support, repair, and healing ofthe internal corneal wound. Modern surgical techniques prevent much ofthe peripheral anterior synechia formation seen in the past. Under these circumstances, the importance of the role of the iris in the healing of the corneal wound becomes apparent.

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