Pseudophakic bullous keratopathy (PBK) and aphakic bullous keratopathy (ABK) refer to the development of irreversible corneal edema as a complication of cataract surgery.[1] As corneal edema progresses and worsens, first stromal and then intercellular epithelial edema develops. Epithelial edema is associated with the development of bullae; hence, the name bullous keratopathy.
![]() View Image | Pseudophakic bullous keratopathy. Large multiple bullae, such as depicted here, are associated with moderate to severe pain and discomfort. |
The history of PBK parallels the history of the development of the intraocular lens. As surgical techniques and lens design have improved, the incidence of this complication has decreased dramatically. However, it still represents an important cause of visual disability following routine and complicated cataract surgery.
Corneal transparency is, in a large part, dependent on the ability of the cornea to remain in a dehydrated state. It is affected by several interdependent factors. The epithelium and the endothelium are semipermeable membranes that create a barrier to the flow of water and other electrolytes into the cornea. Evaporation from the corneal tear film results in slightly hypertonic tears that tend to draw fluid out of the cornea. Intraocular pressure tends to drive fluid into the cornea. Osmotic forces and the electrolyte balance within the corneal stroma also tend to draw water into the cornea. However, the most important influence on corneal deturgescence is the presence of an active metabolic pump in the endothelium.
The endothelium is a single layer of cells present on the back of the cornea. The site of the metabolic pump is within the lateral cell membrane; it is temperature dependent, it is associated with the enzyme Na+/K+ ATPase, and it is inhibited by ouabain. Endothelial cells produce a basement membrane (the Descemet membrane), and they are of neuroectodermal origin. Cell density at birth can be as high as 7500 cells/mm2, decreasing to an average of about 2500-2700 cells/mm2 in older adults.
Endothelial cells are not capable of significant mitotic activity. The normal rate of endothelial loss after age 20 years is approximately 0.5% per year. Surgical trauma, inflammation, and corneal dystrophies can accelerate this normal aging loss. The final common pathway in the development of bullous keratopathy is damage to the corneal endothelium; when the cell density reaches a critically low level of about 300-500 cells/mm2, corneal edema develops.[2]
United States
The exact incidence of PBK is unknown; however, it is estimated that 0.1% of patients undergoing cataract surgery will develop this problem. It is higher is patients with Fuchs dystrophy with a rate of PBK requiring endothelial keratoplasty of 3.3% at 1 year after cataract surgery.[3]
The US Food and Drug Administration (FDA) premarket approval studies for intraocular lenses performed from 1978-1982 found an incidence of postoperative corneal edema of 0.06% for posterior chamber lenses, 1.2% for anterior chamber lenses, 1.5% for iris fixated lenses, and up to 4% for scleral fixated lenses.[4, 5, 6] [7] Certain styles of intraocular lenses introduced in the mid 1980s were reported to have an incidence as high as 5% (eg, Leiske and Hessburg closed loop anterior chamber intraocular lenses, ORC Stableflex, Azar model 91Z).[8, 9]
![]() View Image | Pseudophakic bullous keratopathy. This patient has a closed-loop anterior chamber intraocular lens (Leiske model). |
From 1984-1989, ABK and PBK accounted for most corneal transplants (about 33%) performed in the United States. Since then, the number of cases has decreased, despite an increase in the number of overall cataract surgeries performed. Keratoconus surpassed PBK in 1990 as the leading indication for corneal transplantation in some studies in the United States.[10, 11] This overall drop in the incidence of PBK reflects the rapid development and improvement of both intraocular lens design and cataract surgical technique.
International
Trends similar to that in the United States have been noted in Canada, United Kingdom, Australia, and Scandinavia.[12, 13, 14, 15]
No known association of PBK with race exists.
Patients of Northern European descent do have an increased incidence of Fuchs corneal dystrophy. This dystrophy does predispose to the development of corneal edema (see Pathophysiology, Causes, Histologic Findings).
No known association of PBK with sex exists.
Fuchs corneal dystrophy, a known predisposing factor in the development of postoperative corneal edema, occurs approximately 3 times more frequently in women than in men.
Older patients who have less endothelial reserve are more prone to develop this problem.
Prognosis is good following surgical intervention for PBK. Corneal transplant is a definitive treatment. It can be done in the form of penetrating keratoplasty (PK), Descemet membrane endothelial keratoplasty (DMEK), or Descemet stripping automated endothelial keratoplasty (DSAEK). A patient who undergoes EK can expect mean corrected distance visual acuity (CDVA) 20/25 to 20/30 at 1 year after DSAEK, and 89% of DMEK patients can expect CDVA ≥20/25 also at 1 year.[16, 17]
Symptoms of bullous keratopathy and corneal edema include the following:
Stromal edema affects vision much less and causes less light scatter than epithelial edema; epithelial edema involves the corneal surface and disrupts the normally smooth and regular tear film. The development and subsequent rupture of corneal bullae on the densely innervated corneal surface cause pain and photophobia.[18]
Vision will be decreased in proportion to the development of central corneal edema. Slit lamp examination invariably reveals folds in the Descemet membrane and obvious overall thickening of the central and peripheral cornea.
In the more advanced stages of PBK, vesicles and bullae can be seen on the corneal surface.
In patients with predisposing corneal problems (eg, Fuchs dystrophy), cornea guttata may be seen. On slit lamp examination, guttate excrescences may appear as diffuse fine brownish pigment granules or, in more advanced cases, dense golden-brown confluent endothelial lesions and give the posterior corneal surface a characteristic beaten-metal appearance.
Causes of corneal edema include the following:
Surgical trauma at the time of cataract surgery can be associated with a marked reduction in endothelial cell counts.[21, 22, 23, 24, 25]
With modern techniques of cataract extraction (eg, phacoemulsification) using ophthalmic viscosurgical devices, the rate of endothelial cell loss is reported to be about 2-7%. It varies greatly and is significantly associated with the cataract grade and anterior chamber depth. Diabetes also is a risk factor for endothelial damage. [26]
Endothelial cell loss has been correlated with cataract incision size and location, density of nucleus, total ultrasound energy used, and volume of fluid irrigated into the eye at the time of surgery. Individual surgeon techniques and skill vary widely, and, correspondingly, endothelial cell loss will vary.[27, 28, 29]
Directly touching the endothelium during cataract surgery with instruments, nuclear fragments, or the intraocular lens should be avoided. Routine use of viscoelastic agents has resulted in a dramatic decrease in endothelial cell loss and offers a practical and effective means of protecting the cornea from inadvertent trauma during cataract surgery.[30] Dispersive viscoelastics may offer more protection to the endothelium than cohesive viscoelastics, especially if the surgeon's technique is such that nuclear fragments are removed with phacoemulsification more anteriorly, above the iris plane. Minimization of excess fluid currents, limitation of total surgical time and irrigation time, maintenance of tight primary and secondary wound openings without external reflux, and overall reduction of total balanced salt solution (BSS) use per case all are tactics to reduce endothelial trauma through surgical technique.
Retained lens fragments after phacoemulsification surgery also commonly present with focal corneal edema and rarely can evolve to corneal decompensation requiring transplantation if not removed in time.[31, 32]
Older-style intraocular lenses have been associated with accelerated endothelial cell loss following cataract surgery.
In particular, closed-loop anterior chamber intraocular lenses (ie, Leiske, Hessburg, Azar 91Z style) have been implicated with this problem. The haptics with these lenses tended to be stiff and erode through uveal tissue, causing chronic low-grade inflammation and continued endothelial cell loss. In addition, anterior flexion of the IOL due to the stiff haptics brings the optic into close approximation of the endothelium, with augmented irritation during eye rubbing. Inappropriately large anterior-chamber IOL diameters for a given white-to-white diameter exacerbate both problems.
These IOL designs are thought to be partly responsible for the epidemic of PBK of the mid-1980s. These lenses no longer are implanted. Modern flexible open-loop anterior and posterior chamber intraocular lenses have proven to be much safer alternatives. Biocompatible materials (eg, polymethylmethacrylate, acrylic, silicone), excellent finish, and good flexibility characterize these lenses.
Corneal dystrophies (eg, Fuchs endothelial dystrophy) sometimes are overlooked on the preoperative examination, where the finding of cornea guttata may be subtle, particularly when there is minimal endothelial pigmentation.[33]
![]() View Image | Fuchs endothelial dystrophy. The apparently empty spaces are occupied by guttate. |
Fuchs dystrophy is more common in women than in men and usually presents in older patients. The pattern of inheritance is not known with certainty, but it is thought to be autosomal dominant. Characteristics of this dystrophy include cornea guttata, which are droplike excrescences produced by the endothelium, a thicker than normal Descemet membrane, and a decreased number of endothelial pump sites.[34]
An increased frequency of cornea guttata in the opposite unoperated eye in patients developing PBK has been noted. In one study, 67% of corneal buttons removed at the time of keratoplasty for bullous keratopathy from eyes with posterior chamber lenses (suggesting an intact posterior capsule and uncomplicated cataract surgery) were noted to have evidence of an endothelial dystrophy. Predictive modeling using pachymetry and elevation maps detecting Fuch’s dystrophy features such as loss of regular isopachs, displacement of the thinnest point, and posterior surface depression has shown that the risk of requiring EK after phacoemulsification can be as high as 76.5% in eyes with all of these 3 features.[35]
This highlights the need for a careful preoperative slit lamp examination to help identify patients at risk for the development of postoperative corneal edema. If cornea guttata are noted on slit lamp examination, specular microscopy and ultrasound pachymetry should be performed to help quantify endothelial reserve and to aid in risk assessment. In such patients, the intraoperative use of balanced salt solution plus glutathione, bicarbonate, and adenosine (BSS plus) and dispersive viscoelastic agents may limit endothelial damage.
Patient counseling is essential to manage expectations, including the decision of whether to perform combined endothelial keratoplasty (eg, Descemet membrane endothelial keratoplasty [DMEK] or Descemet stripping endothelial keratoplasty [DSEK]) or to defer the decision on whether to perform the transplant until after the cataract surgery has been performed.
Recently, combined procedures have been found to not differ significantly from staged procedures in complication rates, endothelial cell loss, graft success, or visual improvement. Moreover, combined procedures are easier for the patient, more cost-effective, and do not increase the risk for complications.[36]
The choice of intraocular irrigating fluid can have an effect on postoperative corneal edema.
Under experimental conditions, normal saline induces more corneal swelling than Ringer's lactate solution, whereas BSS causes the least amount of swelling. BSS contains an electrolyte balance very similar to aqueous humor. BSS plus probably is the best solution for use in compromised corneas and when long case times are anticipated (eg, synechiolysis, iris retractors, vitrectomies).[37, 38]
Glutathione is a free radical scavenger and antioxidant, and its use with BSS has been shown to result in the least amount of corneal edema compared with any other intraocular irrigating solution.
The use of intraocular solutions for specific purposes generally has proven to be safe in terms of endothelial cell loss and toxicity.[39] These solutions include intracameral lidocaine for topical cataract anesthesia, Miochol and Miostat for pupillary miosis, epinephrine or phenylephrine combined with BSS and lidocaine to induce mydriasis at the beginning of cataract surgery, or Omidria (Omeros) to maintain mydriasis throughout cataract surgery, or intracameral antibiotics such as cefuroxime and moxifloxacin. However, the use of such solutions should be intelligently conserved, and the principal of the least amount of solution irrigated into the eye to accomplish the stated purpose should be followed.[40]
Episodes of toxic anterior segment syndrome (TASS) have brought the issue of the safety of irrigating solutions used in the eye to the forefront. An excellent review of toxic anterior segment syndrome can be found in References.[41]
Inflammation, specifically iritis and uveitis, can profoundly affect endothelial function.[42]
Classic examples include corneal transplant rejection and herpetic disciform keratitis. In both of these examples, the endothelial cells are the targets of the inflammatory response. However, even nonspecific inflammation, such as that occurring in postoperative and traumatic iritis and other causes of uveitis, can be associated with compromised endothelial function.
If a patient with previous corneal transplant and a history of herpetic keratitis in the operated eye presents with corneal edema and keratic precipitates, noting the location and boundary of the inflammatory process can help distinguish between the two. Inflammation that respects the corneal transplant graft-host wound margin is more likely to be a rejection reaction. If the host cornea and graft host interface are involved, this is more likely to be a recurrence of herpetic infection or stromal keratitis.
Judicious use of topical steroids (eg, prednisolone acetate, loteprednol etabonate, difluprednate, dexamethasone) can have a beneficial effect on corneal edema. This beneficial effect always must be balanced against the possible adverse effects of glaucoma, cataractogenesis, herpetic reactivation, delayed wound healing, and local immunosuppression.
Intraocular pressure has an important effect on the state of corneal hydration.
High intraocular pressure, such as that occurring in attacks of narrow-angle glaucoma, drives fluid into the cornea and is associated with the acute onset of corneal edema, even when the corneal endothelium is otherwise healthy. Conversely, prephthisical eyes with low intraocular pressure may have clear corneas, regardless of endothelial cell count and function.
Lowering intraocular pressure can decrease corneal edema and thickness in the postoperative setting, even if the intraocular pressure is normal or only mildly elevated. Beta-blockers (eg, Timoptic, Betagan) and alpha-agonists (eg, Iopidine, Alphagan) are the first line of therapy for this purpose. Prostaglandin analogs (eg, Xalatan) and miotics (eg, pilocarpine) may adversely affect intraocular inflammation and are recommended to be used with caution. Articles have suggested that topical carbonic anhydrase inhibitors should be avoided in this instance owing to the question of endothelial toxicity in compromised corneas. A newer medication class such as Rho kinase inhibitor (eg, Rhopressa) also has been reported to be associated with reticular epithelial corneal edema.[43, 44, 45]
Postoperative factors that can be associated with endothelial cell loss include vitreous touch and flat anterior chamber with intraocular lens touch.
If the posterior capsule is ruptured at the time of cataract surgery, vitreous may bulge forward into the anterior chamber. Careful vitrectomy at the time of surgery usually prevents prolonged contact of vitreous with the endothelial surface.[46] However, if vitreous is noted to be in contact with the posterior cornea in the early postoperative period, serial pachymetry and specular microscopy can aid in determining if a vitrectomy is necessary.
Removal of the vitreous via a pars plana approach may be beneficial in preventing progressive endothelial cell loss. Similarly, a flat anterior chamber in which the intraocular lens shifts forward and touches the endothelium should be addressed by reforming the anterior chamber as soon as practical. Such a situation may arise if a wound leak or choroidal effusion is present.
Factors limiting vision include a high association of this condition with cystoid macular edema, postoperative astigmatism, uveitis, and glaucoma.
Specular microscopy represents a photographic method of assessing the endothelium in vivo. Light is projected onto the cornea, and reflected images from an optical interface (eg, endothelium, aqueous humor) can be visualized.
High magnification photographs are taken of the endothelial layer, allowing quantification of cell density. Normal cell density varies from 3000-3500 cells/mm2 in young adults to 2700-2900 cells/mm2 in older individuals.[47] Endothelial cells are not capable of significant mitotic activity. The normal rate of endothelial loss after age 20 years is approximately 0.5% per year. Surgical trauma, inflammation, and corneal dystrophies can accelerate this normal aging loss. The final common pathway in the development of bullous keratopathy is damage to the corneal endothelium; when the cell density reaches a critically low level of about 300-500 cells/mm2, corneal edema develops.[2]
Instruments digitize and analyze these photographs, assessing such parameters as the coefficient of variation and the percentage of normal hexagonal cells present. Both of these numbers represent a way of measuring polymorphism and polymegethism (ie, variation in cell size and shape) in the endothelial layer. Endothelial cells that show a great variability in size and shape are considered to be under physiologic stress and abnormal.
Besides evaluating the risk for the development of postoperative corneal edema, specular photomicrographs can be useful as a diagnostic aid to assess corneal disease states (eg, Fuchs corneal dystrophy, posterior polymorphous dystrophy). The former is associated with characteristic guttate excrescences, whereas the latter may show patchy areas of normal endothelium adjacent to abnormal endothelium, as well as vesicles and plaques. Fuchs dystrophy characteristically is most severe centrally with decreasing guttata density and gradually improving cell counts peripherally. Serial specular photomicrographs can be used to follow patients at risk for progressive endothelial loss, such as that occurring with vitreous prolapse into the anterior chamber with corneal touch and corneal transplant rejection episodes.
![]() View Image | Specular microscopy of a normal cornea. Note the compact, uniform hexagonal appearance of the endothelial cells. |
![]() View Image | Specular microscopy illustrating moderate polymegathism and polymorphism. This is thought to be evidence of endothelial physiologic stress. |
Both ultrasound and optical pachymetry are methods of measuring corneal thickness. Normal corneal thickness measures about 0.55 mm centrally, increasing to about 0.8 mm in the corneal periphery. Disease states resulting in corneal edema are associated with central corneal thickening as the cornea begins to swell.
Serial measurements are helpful in gauging the progression of a disease process (eg, Fuchs dystrophy), as well as in assessing a given therapeutic regimen (eg, topical steroid use in corneal graft rejection).
Topography is very useful in evaluating corneal surface changes. Placido disc topography uses rings of alternating dark and light circles, called mires, directing it onto the corneal surface. Its reflection is recorded to qualitatively visualize the surface of the cornea.
Slit-scanning elevation tomography, on the other hand, can image both the anterior and posterior surfaces. A slit beam of light is directed onto the cornea, and the different refractions from the anterior and posterior surface create two reflections. These two reflections can be interpreted using mathematical equations to recreate the surfaces of the cornea. Slit-scanning elevation tomography can help calculate the thickness of the cornea. [48]
Optical coherence tomography (OCT) is a high resolution cross-sectional imaging modality. It initially was developed for retinal imaging but also can be used to precisely evaluate anterior segment structure. In eyes with extensive edema that precludes thorough clinical examination, AS-OCT can help evaluate for corneal thickness, Descemet’s membrane detachment, and corneal scarring.[49]
Pathologic findings noted on corneas removed and replaced for PBK include attenuation and absence of normal endothelial cells.[50] Occasionally, evidence of preexisting endothelial dystrophy (eg, Fuchs dystrophy) may be seen. This dystrophy sometimes is missed during the preoperative exam and, as such, is associated with the development of unexpected and uncounseled postoperative corneal edema. The hallmark of this dystrophy is the finding of corneal guttate (Latin for drop) excrescences and a thickened Descemet membrane. Cornea guttate appear as excrescences extending from the Descemet membrane toward the anterior chamber.
Medical therapy of PBK consists of attempting to minimize corneal edema and the associated symptoms of discomfort and poor vision. Patients with mild disease may benefit from the use of hypertonic agents, such as sodium chloride 2% and 5% solution and ointment. These agents work by creating a hypertonic tear film, thereby drawing water out of the cornea. Because evaporation from the tear film is minimal at night with the eyes closed (therefore, the tears are less hypertonic), corneal edema tends to be worse in the morning. Use of hypertonic sodium chloride 5% ointment at night applied to the conjunctival cul-de-sac may limit this build-up of edema. Use of hypertonic solutions in the morning also may help eliminate some of this nightly fluid accumulation. Some clinicians even recommend a gentle hair dryer to the cornea in the morning to accelerate corneal deturgescence and therefore improved vision.
The benefit of hyperosmolar eye drops is associated with increased duration and frequency of use.[51] Side effects such as burning, dryness, and redness are common with hyperosmolar eye drops.
One regimen for Muro 128 2-5% drops is to instill drops hourly in the affected eye until noon (4-5 times). As the day progresses, evaporation from the tear film begins to create relative hypertonicity of the tears, drawing fluid from the cornea. This accounts for the typical history of improving vision toward the end of the day.[52]
Other practical methods of limiting corneal edema in eyes with borderline endothelial function include treatment of both ocular inflammation and elevated intraocular pressure (see Pathophysiology, Causes) if present.
Bandage contact lenses may be useful as an adjunct to medical treatment for the temporary relief of corneal pain and discomfort. They act to shield the cornea and epithelium from the eyelid. In general, thin, high-water content lenses are tolerated best because they are more oxygen permeable. However, contact lens wear, especially overnight wear, can be associated with increased corneal edema due to improper fit (tight lens) and an increased risk for infection in an already compromised cornea. Patients for whom a bandage lens is prescribed should be treated with a broad-spectrum antibiotic (eg, Polytrim, moxifloxacin) 2-4 times a day. These patients require close follow-up care. Long-term use of a bandage lens for the treatment of this condition is not advised.
Patients who have poor visual potential and severe pain sometimes can benefit from anterior stromal puncture.[53] A 25-gauge needle is used to place multiple small superficial punctures in the affected area of the cornea. The depth of the puncture site is just at or below the Bowman layer. The epithelium subsequently scars firmly over the treated area. This often results in resolution of bullae and pain relief. A bandage lens should be placed over the cornea for 1-2 weeks to allow the epithelium to adhere to the underlying cornea. Excimer laser phototherapeutic keratectomy also has been used to achieve this effect, as has epithelial debridement or lamellar keratectomy.
Corneal cross linking has emerged as a tool in the management of PBK. It has been found to improve corneal transparency, corneal thickness, and ocular pain after surgery. The effect, however, is temporary and decreases with time. Case selection therefore is very important with more effect seen in patients with a thinner CCT (< 700 um) at presentation.[54, 55, 56]
Definitive treatment of PBK and ABK is a corneal transplant.[57, 39] Corneal transplantation is indicated when vision is decreased significantly by corneal edema or when pain becomes intractable. Although a complete discussion of corneal transplantation is beyond the scope of this article, certain unique aspects of corneal transplantation in this setting should be emphasized. First, the size of the graft should be as large as practical without increasing the risk of placing the graft too close to the limbus, thereby increasing the risk for graft rejection. This generally means a donor graft size of 8.00-8.50 mm. Increasing the donor graft size means that more of the healthy endothelium is transplanted. In addition, grafts with higher initial cell counts, 2500-3000 cells/mm2, are desirable for the same reason.
Another important consideration is the management of a preexisting intraocular lens.[58, 59, 60, 61]
Closed-loop anterior chamber intraocular lenses and iris clip style lenses should be removed because of their high association with continued endothelial cell loss and the potential harm to the donor cornea. Special techniques have been devised to remove the often scarred and embedded haptics of closed-loop anterior chamber intraocular lenses with the goal of minimizing iris and angle trauma and associated bleeding.
Well-positioned and appropriately sized flexible haptic anterior chamber intraocular lenses can be left in the eye or exchanged for a posterior chamber intraocular lens. Modern posterior chamber intraocular lenses can be safely left in the eye. A complete discussion of the options for replacement (intraocular lens exchange) are beyond the scope of this article. However, current options include (1) using a modern flexible loop anterior chamber intraocular lens, (2) placing a three-piece posterior chamber lens in the ciliary sulcus, (3) suturing a posterior chamber lens to the iris, (4) suturing a posterior chamber lens in the sulcus with Gore-tex or other sutures, (5) externalizing the haptics of a posterior chamber intraocular lens, inserting them under scleral flap into a scleral tunnel and gluing the flap over the haptic as described by Agarwal et al [62] or (6) externalizing the haptics through transconjunctival sclerotomies, then anchoring them in the sclera by the flange created at the end of the haptics via low temperature cautery (Yamane technique).[63] Implantation techniques begin with careful removal of any anterior displaced vitreous and an equally careful lysis of iris synechiae.
Flexible haptic anterior chamber lenses should be reserved for those eyes with minimal anterior segment pathology, less than 90° of angle synechiae, and well-controlled intraocular pressure.[64, 65] Determining the correct width to implant is essential in preventing complications, such as iris tuck and ovaling (too large), as well as spinning or displacement of the lens (too small). Generally, the width chosen should correspond to a measurement of the horizontal white-to-white corneal diameter plus 1 mm. If inspection of the ciliary sulcus through gentle retraction of the iris reveals an intact and adequate capsular rim, then a posterior chamber intraocular lens can be inserted in the sulcus without suturing the lens in place.[66]
In iris fixation technique, a foldable, three-piece PCIOL is passed behind the iris and a 10-0 polypropylene suture is used to imbricate the haptics into the iris. This technique, however, can produce long-term complications of chronic inflammation including UGH syndrome and pigment dispersion from the iris rubbing on the implant. Prolene suture also breaks down over time with a rate as high at 20% in some studies requiring re-operation.[67] In the scleral fixated IOL technique, many surgeons are adopting the sutureless methods. The two most popular ways to secure the posterior chamber implant to the sclera without sutures are the glued IOL technique and the Yamane technique. In 2007 Agarwal et al first described the glued IOL technique where the haptics of a three-piece IOL were externalized after being passed through two sclerotomies spaced 180 degrees apart. They are secured by tucking each haptic end into a tunnel. Glue is then applied to the haptics and the flaps are replaced over them. In 2016, Yamane et al described a sutureless, flanged haptic technique that also externalizes the haptics of a three-piece IOL through two sclerotomies. The haptics then are secured by creating a flange with low-temperature cautery at the end of each haptic that prevents it from sliding back into the posterior chamber.
A meta-analysis by Lau et al in 2022 found that there was no significant difference in the mean corrected distance visual acuity at the final follow-up between scleral fixated IOL(SFIOL) and Iris fixated IOL (IFIOL) implantation. Although the incidence of vitreous hemorrhage was significantly higher and the final endothelial cell count ECD was significantly higher in the SF IOL group, there were no differences in visual acuity and refractive outcomes between SF IOL and IF IOL. A significantly greater proportion of patients also experienced pupil distortion following IFIOL relative to sutureless SFIOL implantation.[68]
Many different variations of these techniques have evolved along with micro-instrumentation and intraocular lenses. It is up to the individual practitioner to determine which of these lens implant options is most appropriate for a given patient; however, it is important to note that no study to date has clearly pointed to an advantage of one technique or style of intraocular lens replacement in terms of corneal transplant survival, vision, or development of secondary complications.
Endothelial keratoplasty (EK) options include Descemet membrane endothelial keratoplasty (DMEK) and DSAEK (Descemet Stripping Automated Endothelial Keratoplasty). The choice of whether to perform DMEK or DSAEK may depend upon surgeon preference and patient characteristics including anterior segment disease, intraocular lens status and location, iris defects, history of vitrectomy, and prior glaucoma surgery. The method of insertion of DMEK and DSAEK grafts can damage the donor corneal endothelium, and there are different techniques for insertion.[69]
DSAEK (Descemet Stripping Automated Endothelial Keratoplasty) begins by stripping off and removing the patient's central endothelium and Descemet’s membrane (Descemet stripping). A posterior lamellar disc is prepared by placing a donor cornea in an artificial anterior chamber and cutting it with a microkeratome. Eye banks can provide surgeons with precut corneal tissue for DSAEK surgery. The thickness of DSAEK grafts has decreased over time and many surgeons now use ultra-thin (50-100 microns) or nano-thin (less 50 microns) tissue. The donor graft is folded and inserted into the eye, where it is subsequently unfolded and elevated up against the patient's cornea with an air bubble. The bubble then is partially removed at the end of surgery.[70] The patient lies flat in the supine position after surgery to allow the donor disc to attach to the host cornea.
A newer modification of endothelial keratoplasty is called Descemet membrane endothelial keratoplasty (DMEK). In this procedure, an ultra-thin graft consisting of only Descemet’s membrane and endothelium from a donor is used to replace the recipient endothelium. Eye banks can prepare DMEK grafts for surgeons. The donor graft in DMEK is inserted into the eye and unfolded. Air or gas is used to elevate the graft and attach it to the host cornea. The patient lies flat in the supine position after surgery to allow the graft to attach to the host cornea. DMEK has been adopted by many corneal surgeons, and newer techniques have helped flatten the learning curve and overcome the technical difficulties of manipulating and unfolding the donor graft.[71, 72]
Compared with traditional DSAEK surgery, DMEK offers more rapid visual recovery, better visual acuity outcomes, and a decreased risk for rejection. In a first series of 50 DMEK surgeries performed for Fuchs endothelial dystrophy, 95% had a best-corrected visual acuity of 20/40 or better (≥0.5) and at 6 months 75% reached 20/25 or better.[73] However, many surgeons now use thinner DSAEK grafts. The Descemet Endothelial Thickness Comparison Trial (DETECT), which was a randomized, masked study that compared DMEK and ultra-thin DSAEK, found that DMEK patients had better visual acuity 24 months after surgery but may have had higher endothelial cell loss and more complications than ultra-thin DSAEK patients.[73] A larger, multicenter DETECT study will determine if differences exist in visual acuity, graft survival, complications, and endothelial cell loss after DMEK versus ultra-thin DSAEK.
In terms of graft rejection, the risk for an immunologic rejection episode is significantly lower with EK than PK. EK rejection episodes also are milder and less likely to progress to graft failure than PK rejection episodes.[74] A study found that at 2 years, the cumulative rejection risk was 2% with DMEK, 12% with DSEK, and 18% with PK when performed for similar indications.[74] Another comparative study found that at 5 years the reported cumulative graft rejection rates of 1.7% with DMEK, 5% with DSEK, and 14% with PK performed for similar indications.[75]
In the absence of other corneal disease or opacity, full-thickness penetrating keratoplasty (PK) no longer is performed for PBK and ABK. The advantages of endothelial keratoplasty techniques (DMEK, DSAEK) include quicker visual recovery, better visual outcomes, decreased risk for rejection, preservation of the natural topography and prolate corneal contour, and a much smaller incision, with improved wound strength, comparable to that seen with small-incision cataract surgery. The patient's own corneal curvature is preserved, with less induction of astigmatism.
The goal of pharmacotherapy is to reduce morbidity and to prevent complications.
Clinical Context: For osmotic pressure control and water distribution.
May reduce inflammation in cornea by creating an osmotic gradient across an intact blood barrier.
Clinical Context: Used for ocular infections involving cornea or conjunctiva resulting from strains of microorganisms susceptible to this antibiotic combination.
Clinical Context: Polymyxin B is used for ocular infection of the cornea or conjunctiva caused by susceptible microorganisms.
Clinical Context: Bacitracin prevents transfer of mucopeptides into the growing cell wall, which causes inhibition of bacterial cell wall synthesis. Polymyxin B damages bacterial cytoplasmic membrane and alters permeability, causing intracellular constituents to leak.
Clinical Context: This ophthalmic macrolide antibiotic is indicated for bacterial conjunctivitis caused by susceptible strains of microorganisms and for prevention of corneal and conjunctival infections.
Empiric antimicrobial therapy must be comprehensive, covering all likely pathogens in the context of the clinical setting.
Clinical Context: Treats acute inflammations following eye surgery or other types of insults to the eye.
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
These have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Clinical Context: Selective alpha 2-receptor that reduces aqueous humor formation and increases uveoscleral outflow.
Clinical Context: These may reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor or by outflow.
These agents reduce elevated and normal intraocular pressure, with or without glaucoma.