Device Assembly

The donor cornea in the Boston KPro acts as a peripheral carrier and interface to facilitate suturing of the device to the host. In contrast to PK, optical clarity and a viable endothelium are not required in donor tissue procured for the use in Boston KPro implantation. Frozen tissue carriers demonstrate similar visual rehabilitation and complications rates as fresh tissue. Success has also been reported with the use of gamma-irradiated human corneal tissue. ²⁵

The donor cornea is fashioned in a donut configuration using two concentric punches. The donor cornea is cut using 8.0- to 9.0-mm trephine and should aim to oversize the recipient trephination by 0.25 mm. The technique is the same as for PK.

The donor button is then placed endothelial side up on a sterile table in preparation for the inner trephination. A central corneal button is excised using a 3-mm handheld dermatological punch. The punch is carefully centered over the graft and twisted slowly while applying constant downward pressure.

The anterior plate of the device is placed anterior side down on a cushion of viscoelastic on a sterile table. The 3-mm central hole of the donor cornea is lowered over the stem of the front plate endothelial side up and gently secured in place. The backplate is then centered over the stem of the front plate, effectively sandwiching the donor cornea between the two plates. The threadless “snap-together” design obviates the need for rotational movements. The latest configuration of the device has a locking component incorporated into the backplate.

The final assembled device should be examined under the surgical microscope to verify that all components are correctly and securely aligned.

Preparation of the Recipient Bed

The recipient bed is prepared according to the same principles as standard PK. Ideally, the host trephination should successfully encompass the diseased cornea, but in practice, the size is limited by proximity to the anterior chamber angle. As previously mentioned, the recipient trephine should be 0.25 mm smaller than the selected diameter of the donor corneal button. If present, iridocorneal adhesions can be lysed. The device is secured to the recipient bed with multiple interrupted 9–0 or 10–0 nylon sutures (16–24), which are passed through the corneal donor button portion. All suture knots are buried. The graft–host junction should be watertight at the end of the procedure.

The procedure is performed either under general anesthesia or monitored intravenous anesthesia. Intravenous antibiotics are recommended at the time of surgery. At the completion of surgery, a large plano soft contact lens is placed on the eye.

Additional Procedures

The primary KPro surgery is often combined with other procedures, including lensectomy, IOL removal, iridoplasty, glaucoma filtration devices, and anterior chamber or pars plana vitrectomy.

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  Lens: If the patient is phakic, lensectomy is performed at the time of Boston KPro type I surgery, given the inevitable development of postoperative cataract and the complexity involved in removing a cataractous lens in the setting of a Boston KPro type I device. ²⁶ A number of factors conspire towards cataract formation postoperatively, including surgical trauma, postoperative inflammation, and long-term topical steroid use. The posterior capsule is preserved and an aphakic KPro is implanted.

Stable posterior chamber IOLs may be left in situ, but unstable lenses and anterior chamber lenses should be explanted. Glued IOL can be combined with KPro (▶Fig. 7.2). An aphakic KPro is available for aphakic eyes. A thorough core vitrectomy must be performed in all eyes at risk of vitreous presentation.

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  Glaucoma drainage device: A preemptive approach to elevated IOPs should be considered as shunt placement at the time of Boston KPro placement has been associated with both lower rates of de novo glaucoma and secondary procedures to lower IOP, without an increased incidence of intraoperative or postoperative complications. ^{1 , 27}

Pars plana placement of the tube accompanied by a complete vitrectomy is recommended to avoid crowding of the anterior chamber and occlusion of the glaucoma implant from either vitreous incarceration or progressive peripheral anterior synechiae. Furthermore, posterior placement optimizes contact lens fitting. The plate of the GDD is sutured in place prior to opening the eye (▶Fig. 7.3). After implantation of the Boston KPro, the glaucoma shunt is then introduced through the pars plana. Accurate placement of the device should be confirmed by direct visualization. A patch graft should be used to minimize the risk of tube exposure.

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  Vitreoretinal Procedures: Pars plana vitrectomy may accompany Boston KPro implantation to decrease potential posterior segment complications, to accommodate pars plana glaucoma drainage implants, to remove possible platforms for retroprosthetic membranes (RPMs), and/or to reduce potentially proinflammatory material. ²⁸ There is some evidence to suggest that aphakic eyes that undergo total pars plana vitrectomy have fewer postoperative complications such as glaucoma progression and RPM formation than eyes with partial pars plana or anterior vitrectomies. ²⁸ It is postulated that the performance of a pars plana vitrectomy may lower the rates of endophthalmitis and the rates of epithelial downgrowth and subsequent retinal detachment. ²⁷

Postoperative Evaluation

Implantation is the first phase of a lifelong relationship between the patient and the ophthalmologist. KPro eyes require a commitment to postoperative medication and closely monitored follow-up, ideally by a multidisciplinary team consisting of corneal, glaucoma, and retinal specialists. Patients must understand the commitment involved, and the requirement for intensive follow-up should guide patient selection. A generic follow-up regimen would include the day after surgery, 1 week after, 2 weeks after, 1 month after, then every 2 months for the first year, and quarterly thereafter. ⁹ In practice, the follow-up regimen will be influenced by postoperative events and must be customized according to requirements.

The visual acuity should be recorded at each visit and a thorough anterior segment examination should be performed. In particular, the examiner should look for signs of inflammation, RPM formation, corneal melt, wound leak, and epithelial defects. Early opacification of the fenestrations in the posterior plate is suggestive of chronic inflammation. When present, the GDD should be examined for signs of leak, vitreous incarceration, and conjunctival erosion. The position of the tube should be noted.

The position of the BCL should be evaluated. Protein deposits on the surface of the contact lens may necessitate lens replacement sooner than the suggested 3-month intervals.

The appearance of the optic nerve should be carefully documented at each visit. Baseline visual field and OCT of the optic nerve should be performed as soon as feasibly possible as the results may be affected by refractive and ocular media changes as well as glare after Boston KPro implantation. ²⁹ These investigations should be performed more frequently than with standard glaucoma monitoring. Each examination should include an assessment of IOP, typically using digital palpation.

The posterior segment can be directly visualized with a 90- or 78-D lens. The feasibility of wide-field fundus photography through the Boston KPro has been demonstrated, with the best image quality acquired using the noncontact Optos imaging system. ³⁰ OCT of the macula can be performed if cystoid macular edema or other pathology is suspected.

Where available, anterior segment OCT can be used to evaluate the anterior chamber and the configuration of the angle. Ultrasound biomicroscopy may be used to image glaucoma tube shunts, the posterior chamber IOL, and other structures behind the iris plane. ⁷ Advances in imaging techniques have enhanced our understanding of the interaction between the device and the host anatomy. ⁷

Postoperative Treatment

The mainstays of postoperative treatment are long-term prophylactic antibiotics, topical corticosteroids, and BCL wear. However, there are is no consensus regarding the specifics of the regimen. A suggested postoperative management regimen is provided in ▶Table 7.2.

Boston KPro type I eyes are uniquely predisposed to infection. Fortunately, the introduction of long-term prophylactic topical antibiotics has resulted in a significant reduction in endophthalmitis. Indeed, one series reported a 75% decrease in the rate of endophthalmitis, following the widespread adoption of their use. ³¹ However, the optimal postoperative regimen is not universally agreed upon. Treatment schedules should provide coverage for both gram-positive and gram-negative organisms. Typical regimens include a topical fourth-generation fluoroquinolone with or without topical vancomycin. Given that many Boston KPro eyes have a compromised ocular surface, consideration must be given to the toxic–therapeutic ratio. The treatment regimen is discussed in greater detail in the complications section.

Continuous soft contact lens wear has been shown to reduce the rate of postsurgical ocular surface complications after keratoprosthesis implantation. ³² Ocular surface complications are common in Boston KPro type I eyes and can result from surface irregularities, blink abnormalities, and evaporative forces. ³² Their sequelae include delle formation, epithelial defects, stromal thinning, sterile keratolysis with implant extrusion, perforation, aqueous leak, and infection. ³³ A contact lens maintains hydration and helps protect the corneal tissue surrounding the anterior implant from desiccation, epithelial breakdown, and melt. ³⁴ Furthermore, contact lenses can improve comfort and cosmesis and can also correct refractive errors (▶Fig. 7.4). However, continuous contact lens wear comes with its own attendant problems such as lens loss, protein deposits, inflammatory biofilms, chronic conjunctivitis, and infection. ³⁴ Moreover, obtaining an adequate contact lens fit is often challenging in Boston KPro eyes and should be performed by a contact lens specialist. Lenses must be routinely changed, typically every 3 to 4 months; however, no consensus exists as to the ideal schedule.

Chronic low-grade intraocular inflammation is a frequent complication, particularly in autoimmune conditions. ⁶ The sequelae of chronic inflammation include vitreous opacities, RPMs, epiretinal membranes (ERMs), cystoid macular edema, and angle closure glaucoma. Corticosteroids have been used since the inception of the device to prevent inflammation. Topical steroid drops, usually prednisolone acetate 1%, are used postoperatively between four times daily and every 2 hours and tapered over 4 to 6 months. The adverse effects of topical steroids are well established and include IOP elevation, diminished host defenses, and impaired wound healing. Therefore, efforts should be made to cease topical corticosteroids after 6 months in quiescent eyes; however, this is often prevented by the presence of inflammation. Peribulbar triamcinolone injections (20–40 mg) may be considered in circumstances where increased inflammation is suspected, such as the development of RPMs and opacification of the fenestrations in the posterior plate. Systemic doxycycline and topical progestational corticosteroids have also been used to reduce inflammation. ³⁵

Glaucoma

Glaucoma is the most common cause of failure to obtain and maintain visual acuity of ≥20/200. ¹ The pathophysiology of glaucoma development and progression in Boston KPro type 1 eyes is complex and multifactorial. Many of the underlying conditions precipitating Boston KPro type 1 implantation (e.g., aniridia, chemical burns, or multiple previous surgeries) are themselves independently predisposed to glaucoma formation. Indeed, the reported incidence of pre-existing glaucoma in Boston KPro patients ranges from 33.3 to 89.3%. ^{39 , 40 , 41 , 42 , 43 , 44 , 45 , 46} Mechanical disruption of the iridocorneal angle at the time of implantation may further contribute to the risk. Postoperative factors include mechanical compromise and crowding of the iridocorneal angle by the Boston KPro backplate, peripheral anterior synechiae formation, clogging of the trabecular meshwork with cells and debris, intraocular inflammation, and prolonged corticosteroid use. ⁴⁷

The management of glaucoma is complicated by the lack of a reliable method of IOP assessment in Boston KPro type 1 eyes. Scleral dynamics and intraocular fluid dynamics are altered by the KPro, rendering standard applanation and handheld tonometers inaccurate. IOP estimation by digital palpation is a commonly used method; however, it has many disadvantages, including intrinsic imprecision, lack of interexaminer repeatability, and variable alterations in the dynamics of the globe caused by the presence of device hardware. ²⁴ Scleral pneumotonometry may have a role, but again, the Boston KPro type 1 backplate has the potential to interfere with scleral measurement. ⁴⁸ The ideal device would provide a direct record of true IOP, independent of the cornea and sclera. Boston KPro investigators are in the early phases of developing a contactless IOP measurement sensor that is integrated into the optical stem of the Boston KPro device, a micro-optomechanical pressure system.

Given the absence of a reliable method of IOP assessment, frequent evaluation of optic nerve appearance and function is essential in maintaining a long-term vision. Direct visualization of the optic nerve should be supplemented with serial optic nerve head OCT and optic disk photographs. Serial threshold perimetry should be performed to monitor for visual field changes, but may not be possible in eyes with limited vision. Microperimetry maybe a good adjunct to standard perimetry in patients with fixation involvement. ²⁴ In a small series, functional testing with visual fields was found to be more reliable than structural testing to monitor glaucomatous changes, but both can be useful after KPro implantation. ³⁷ The latest Boston KPro type 1 design allows a maximal 95° angle of visual field in nonglaucomatous patients. ²⁹ Anterior segment OCT may also be useful in evaluating angle structures.

The manufacturer of Boston KPro recommends a low IOP target (12 mmHg or less) in all eyes and consideration of prophylactic antiglaucoma medication in eyes without a preoperative diagnosis of glaucoma. ⁴⁹ Clinicians should have a high index of suspicion for the development and/or progression of glaucoma. Topical glaucoma therapy may be initiated prior to surgical treatments; however, they may be less effective in Boston KPro type 1 eyes because of the reduced corneal surface available for drug penetration and the extensive damage to the outflow channels. Furthermore, the potentially cytotoxic effects of these topical medications may exacerbate an already compromised ocular surface. Clinicians should switch to preservative-free formulations where possible. Oral carbonic anhydrase inhibitors have a role but are often limited by side effects.

The constellation of unreliable IOP measurement, poor response to topical antihypertensives, and the high prevalence and severity of glaucoma has led to a low threshold for performing glaucoma surgery, either preoperatively or concurrently with device implantation. ²⁴ However, there is no consensus regarding the best sequence of KPro and GDD procedures. ^{24 , 50} GDD implantation prior to Boston KPro type 1 and post Boston KPro type 1 surgery is challenging due to poor visualization secondary to corneal opacification and the limited view through the optic, respectively. ⁵⁰ Concurrent surgery has the advantage of allowing greater precision in the positioning of the GDD tube and allows the patency and function of the GDD to be accessed. ⁴⁹ Furthermore, it obviates the increased risk and expense associated with two surgical procedures. Currently, the manufacturer of the Boston KPro recommends that a GDD is placed before or concurrently with Boston KPro implantation in all eyes with pre-existing glaucoma. ⁴⁹ Glaucoma surgery performed prior to or concurrently with Boston KPro type 1 implantation has been shown to have significantly slower rates of postoperative cupping compared with eyes that received delayed surgical glaucoma treatment. ⁴² Furthermore, GDD placement at the time of Boston KPro implantation in eyes with pre-existing glaucoma is not associated with an increased incidence of postoperative complications. ^{49 , 51}

The argument for empiric prophylactic placement of a glaucoma shunt is countered by the complications of overly aggressive surgery, including hypotony maculopathy and suprachoroidal hemorrhage. ⁵² Other complications include decreased best-corrected visual acuity, blockage of the tube, tube erosion with subsequent infection, and aqueous leak. Prior to transplant, Boston KPro type 1 candidates should be assessed by a glaucoma specialist. However, an effective glaucoma assessment is often limited by corneal opacification. The more pertinent discriminator may be: which patients are not at risk of increased IOP after KPro? The answer may be limited to those with existing and successful GDDs, pre-existing hypotony, or those with low-normal IOP and healthy optic nerves despite multiple intraocular procedures and a prolonged corticosteroid challenge. ⁵²

Progression of glaucoma results in the need for glaucoma surgery in approximately 5 to 20% of eyes, following Boston KPro type 1 implantation. ^{37 , 42 , 43 , 53 , 54 , 55} Glaucoma surgery post Boston KPro is challenging as there is limited view through the optic, making accurate placement of the tube difficult. Both valved and nonvalved implants have been used with Boston KPro implants. Valved implants have the advantage of less frequent hypotony from overfiltration. Although nonvalved GDD can have more substantial IOP lowering effect than valved GDD, they require several weeks of hypertensive phase to prevent hypotony, which may allow for snuff out to occur.

Cyclodiode photocoagulation has been proposed as an alternative to a GDD as there is no permanent hardware and therefore avoids the risk of exposure and subsequent endophthalmitis. Furthermore, it is a good option if GDD implantation is not possible due to extensive conjunctival scarring. However, cyclodiode photocoagulation is often difficult to titrate, causes inflammation, and may require multiple treatment sessions for adequate IOP control. Excessive treatment can result in hypotony. The procedure can be performed trans-sclerally or endoscopically under direct visualization. A fiberoptic light for trans-scleral illumination can be used to facilitate identification of anatomical landmarks, but excessive scar tissue on the ocular surface may limit the utility of this technique.

Sterile Stromal Necrosis

Corneal melt is a serious complication that may threaten vision and undermine the structural integrity of the eye. Vision loss may arise secondary to device extrusion, endophthalmitis, aqueous leakage, hypotony, choroidal or retinal detachment, and choroidal hemorrhage. ⁵⁶ Nutritional deprivation and ocular surface desiccation have been implicated in the etiology of corneal melt. ⁵⁷ Strategies to address these issues include the addition of small fenestrations in the backplate of the device and the use of a BCL, respectively. Other risk factors for corneal melt include RPM formation, persistent epithelial defects, contact lens intolerance, underlying inflammation, conjunctival deficiency, and previous infectious keratitis. The rate of sterile corneal melting has been reported in various case series to range from 0 to 25.9%. ^{21 , 38 , 39 , 45 , 58}

In the absence of aqueous leakage, conservative treatment measures include proper fitting of a BCL and/or lateral tarsorrhaphy to improve ocular surface wetting. ⁵⁶ Topical or oral matrix metalloproteinase inhibitors, such as tetracyclines or medroxyprogesterone, and intravitreal infliximab can be considered. ⁵⁶ Topical steroid use should be minimized. Surgical techniques to manage corneal melt include cyanoacrylate tissue glue for focal melts, amniotic membrane grafts, suture closure of leaks, lamellar patch graft, Boston KPro removal with replacement with either PK or secondary Boston KPro, and Boston KPro removal with reassembly onto a new cornea for implantation. ⁵⁷

Infection

Postoperative infections are a serious complication with the potential to compromise device retention and visual outcomes after KPro implantation. The proportion of patients developing microbial keratitis after KPro surgery ranges from 0 to 17%, with more recent studies suggesting a declining incidence secondary to improved postoperative care. ³⁶ Microbial keratitis typically presents with an opacity below the edge of the KPro adjacent to the optical stem. ⁵⁹ Cases of microbial keratitis are treated with intensive topical antibiotic therapy with fortified vancomycin (25 mg/mL) and fortified ceftazidime (50 mg/mL), fortified tobramycin (16 mg/mL), or a fourth-generation fluoroquinolone. The antibiotic regimen should be adjusted on the basis of the identification of the bacterial isolate, the susceptibility profile, and the clinical course. If a fungal isolate is identified, intensive topical therapy should be initiated with topical amphotericin B (1.5–5.0 mg/mL) and voriconazole (10 mg/mL). Device explantation is indicated if there are concerns about intraocular extension or evidence of microbial contamination of the device. ³⁵ Endophthalmitis most often progresses consecutive to microbial keratitis. ⁵⁹

The rate of endophthalmitis is one of the highest among ophthalmic surgical procedures with a reported incidence of 2.7% per patient-year. ⁶⁰ In the three series on long-term follow-up of Boston KPro, endophthalmitis developed in 0, ¹ 12.5 ³⁹ and 15.5% of eyes. ³⁸ The device bridges the nonsterile ocular surface and the sterile anterior chamber, providing a portal for the ingress of pathogens. The lack of biointegration of the device further contributes to the risk of endophthalmitis. While the placement of a soft BCL is necessary to maintain ocular surface hydration, the BCL can act as a fomite, further increasing the risk of infection.

Epithelial defects are a common pathway for infection, particularly when they arise at the graft device junction. ³⁵ Eyes with a background of ocular surface disease are also at an increased risk of infection. ³⁵ The rate of infection is higher in eyes with SJS and ocular cicatricial pemphigoid, moderate in chemical burns, and low in noncicatrizing disease. ⁶¹ Other risk factors for infection include drainage blebs, GDDs, and recent intraocular procedures. Exposure of GDD tubes is another high-risk factor that mandates surgical repair, whenever possible. ³⁵

Long-term prophylactic topical antibiotics have been instrumental in reducing rates of endophthalmitis in Boston KPro eyes. However, there is no consensus on the specific regimen. Cases of infectious endophthalmitis in Boston KPro eyes are most commonly secondary to gram-positive organisms, in particular, Staphylococcus aureus, Staphylococcus epidermidis, Streptococci pneumoniae, and other Streptococci species. This observation prompted the addition of topical vancomycin to the antibiotic regimen, which reduced the proportion of cases developing endophthalmitis considerably. However, vancomycin may encourage the selection of gram-negative infections and topical vancomycin for long-term antibiotic prophylaxis has been shown to be associated with an increased incidence of endophthalmitis secondary to gram-negative organisms. ³⁸ It has been suggested that vancomycin itself may alter conjunctival barrier function in KPro cases. ⁶² Furthermore, fungal infections have emerged in Boston KPro eyes, following the introduction of broad-spectrum antibiotic prophylaxis and therapeutic contact lenses (▶Fig. 7.5). ⁶² Two studies that reported zero cases of endophthalmitis both used a fourth-generation fluoroquinolone (moxifloxacin 0.5% or gatifloxacin 0.3%) for prophylaxis. ^{1 , 58} The authors postulated that the reason for the absence of endophthalmitis in their series was likely “myriad but may in part be due to the decision not to use topical prophylactic vancomycin.” ¹

Empiric antifungal prophylaxis is not recommended considering the low rates of fungal infections and that fungal colonization does not predict infection. ⁶² In climates where fungal keratitis is endemic, short cycles of an antifungal agent are recommended. Natamycin 5% or compounded amphotericin 0.15% may be given twice daily for 1 week every 2 to 3 months. ⁷ Antimicrobial management may be augmented with a fornix rinse with 5% povidone-iodine at regular follow-up visits, particularly in conjunction with contact lens replacement or cleaning.

Bacterial endophthalmitis typically presents with a sudden onset of severe eye pain accompanied by an acute reduction in vision. In contrast, fungal endophthalmitis may follow a more indolent course. Suspected cases of endophthalmitis mandate immediate evaluation and treatment. A diagnostic vitreous tap is performed followed by the intravitreal injection of vancomycin (1 mg/0.1 mL) and either ceftazidime (2.25 mg/0.1 mL) or amikacin (0.4 mg/0.1 mL). In cases of suspected fungal endophthalmitis, an intravitreal injection with amphotericin (5 µg/0.1 mL) and voriconazole (100 µg/0.1 mL) is performed. Urgent referral to a vitreoretinal surgeon for consideration of a pars plana vitrectomy is essential. Successful microbiologic and tectonic management of the globe may require removal of the graft and replacement with either another Boston KPro or PK.

Despite immediate and aggressive treatment, the final visual outcomes are often poor, especially when the presenting vision is hand movements (HM) or worse. ³⁵ The outcome is influenced by the causative organism with S. epidermidis associated with better outcomes compared with S. aureus and S. pneumoniae. ⁶¹

Sterile Vitritis

The classical paradigm for sterile vitritis in KPro describes cases of vitritis associated with sudden painless vision loss with full visual recovery upon treatment with periocular corticosteroids. ⁵⁹ However, sterile vitritis may also present with significant eye pain and may not experience a full recovery of visual acuity despite treatment. ⁵⁹ It has a wide spectrum of presentation and may mimic infectious endophthalmitis. The etiology remains unclear and is likely multifactorial. Proposed mechanisms include periprosthetic sterile tissue melt, microbial cell wall or nucleic acid triggering noninfectious inflammation, and systemic immune response. ⁶³ Sterile vitritis, is a diagnosis of exclusion and a vitreous biopsy, followed by intravitreal antibiotics is the standard of care when the clinical picture suggests infectious endophthalmitis. ⁶³ If vitreous cultures are negative and there is no improvement in clinical course, topical or sub-Tenon injection of corticosteroid can be considered. ⁵⁹ The condition may have a protracted course despite corticosteroid treatment and full recovery of baseline visual acuity is not certain. ⁶³

Retroprosthetic Membranes

RPM formation is the most common complication after Boston KPro implantation (▶Fig. 7.6), though the reported incidence varies widely from 1 to 65%. ³⁶ It is unclear why the range is so extreme. RPMs have been associated with a constellation of vision-threatening postoperative complications such as retinal detachment, corneal donor carrier graft melt through the inhibition of nutrient delivery, glaucoma via progressive angle closure, and chronic hypotony secondary to tractional ciliary body membranes. ⁶⁴

Eyes receiving KPro for infectious keratitis and aniridia are at the highest risk of RPM development. ⁶⁵ IOLs have been implicated in the formation of contractile intraocular membranes leading to the aniridic fibrosis syndrome and may further act as a platform for RPM formation. ^{66 , 67} Therefore, it may be necessary to limit the amount of intraocular hardware in eyes with an increased risk of RPM formation. ⁶⁴

Treatment for RPM may include observation when mild, or removal when visually significant with either neodymium–yttrium-aluminum-garnet (N-YAG) laser membranotomy or pars plana vitrectomy. ⁹ Surgical membranectomy is indicated when the RPM is too thick for YAG or vascularized.