Patients with gelatinous drop-like corneal dystrophy need to be effectively managed as the disease is severely debilitating in view of associated pho-tophobia and glare. Here, we report a rare case of gelatinous drop-like corneal dystrophy effectively managed by intraoperative anterior segment optical coherence tomography-guided manual deep anterior lamellar keratoplasty in 1 eye and sutureless fibrin glue-aided, microkeratome-assisted automated lamellar therapeutic keratoplasty in the other eye. The patient, a 22-year old man, presented with gradual diminution of vision associated with foreign body sensation, glare, photophobia, and watering due to corneal lesions, which were consistent with a diagnosis of gelatinous drop-like corneal dystrophy. Visual acuity at pre-sentation was 4/60 and 3/60 in the right and left eye, respectively. The patient received customized component lamellar keratoplasty in both eyes, and host tissue was sent for histopathologic examination. Treatment resulted in a best-corrected distance visual acuity of 6/9 and 6/12 in the right and left eye, respectively. The graft was clear and well apposed, with minimal interface haze bilaterally. The histopathologic report suggested intralamellar amyloid deposition in the form of homogenous, acellular eosinophilic deposits in the epithelium and anterior corneal stroma. This is a first report of the exclusive use of a fibrin-aprotinin tissue adhesive to stabilize a donor corneal lamellar graft as a treatment modality for a patient with gelatinous drop-like corneal dystrophy, suggesting that this treatment could supplant the need for sutures.
Key words : Fibrin glue, Intraoperative optical coherence tomography, Photophobia, Subepithelial amyloidosis, Sutureless lamellar keratoplasty
Gelatinous drop-like dystrophy (GDLD) is a rare corneal epithelial-subepithelial dystrophy charac-terized by an autosomal recessive pattern of inheritance. It has also been referred to as subepithelial amyloidosis or Grayson’s primary familial amyloi-dosis pertaining to the pattern of amyloid deposition seen on histopathologic examination.1 To the best of our knowledge, there has only been a single report of 2 siblings affected with GDLD from India.2
Those with GDLD usually present in the late first or the second decade of life with severe photophobia, glare, foreign body sensation, and watering. Vision is affected as the subepithelial nodular lesions increase with disease progression; these lesions are associated with epithelial erosions and subepithelial scarring, thus severely disabling the patient. Full-thickness keratoplasty and lamellar keratoplasty secured with sutures have been described in the published literature to rehabilitate patients with this condition.3 Here, we report a patient with clinical features of GDLD who was treated with sutureless lamellar keratoplasty aided with an integrated intraoperative optical coherence tomography (iOCT). To the best of our knowledge, there has been no report in the literature describing the successful use of sutureless automated lamellar therapeutic keratoplasty (ALTK) for treatment of corneal lesions in patients with GDLD.
A 22-year-old male patient presented with photo-phobia, glare, watering, and recurrent episodes of pain and redness over the past 4 years with gradual progression. Over the past 18 months, the patient had associated diminution of vision. There was no relevant history of ocular trauma, ocular surgery, and use of any medications. Birth history, perinatal period, and neonatal development were uneventful. Results of a general physical examination and systemic examination were within normal limits. The family history of the patient was significant, as there was a similar history in an older sibling and also his parents had had a consanguineous marriage.
On ocular examination, best-corrected visual acuity (BCVA) was 4/60 OD in right eye and 3/60 OS in left eye with accurate projection of rays. On slit-lamp biomicroscopic examination of the cornea, whitish nodular mulberry-like lesions were seen in the central 5 to 6 mm of the cornea in both eyes, which were translucent on retro-illumination. In the left eye, there was associated subepithelial and stromal scarring. Corneal sensations were intact bilaterally. There was bilateral moderate meibomian gland dysfunction. Anterior chamber depth was normal, and lens was clear in both eyes. On indirect ophthalmoscopy, fundus findings were within normal limits. Anterior segment optical coherence tomography (ASOCT) of both eyes revealed a central corneal thickness of 521 μm OD and 514 μm OS, respectively. In the right eye, superficial involvement of the corneal layers was seen (up to 175-220 μm), whereas in the left eye scarring was noted up to a depth of around 400 μm (Figure 1).
Visual rehabilitation of the patient was planned by performing lamellar keratoplasty in both eyes. The patient underwent left eye iOCT-guided (OPMI LUMERA 700 and RESCAN 700, Carl Zeiss, Meditec, Germany) manual deep anterior lamellar keratoplasty (DALK) in view of significant stromal scarring associated with the superficial lesions (Figure 1). Five months later, the right eye underwent a sutureless fibrin glue-aided, microkeratome-assisted ALTK under continuous intraoperative ASOCT (OPMI LUMERA 700 and RESCAN 700, Carl Zeiss) guidance (Figure 2). After presurgical preparation, the depth of the opacity in the right eye was reconfirmed with the use of iOCT; after depth of opacity was confirmed as 230 μm deep, the donor tissue was mounted on the Gebauer ALTK artificial anterior chamber (Gebauer/Medizintechnik GmbH, Neuhausen, Germany). The donor tissue was cut using a 250-μm microkeratome head to obtain a partial thickness donor lenticule (free cap), which was kept safely in McCarey-Kaufman corneal storage medium. This automated system provides a nonhinged anterior corneal lamellar lenticule that is totally free from the posterior donor lamella mounted on the artificial chamber (Figure 2D).
Dissection of host tissue was then done using a Gebauer automated microkeratome using a 250-μm blade. The dissected recipient bed was measured to be 9 mm in diameter; therefore, the donor tissue lenticule was subsequently trephined to the same size. After the recipient bed received a thorough wash to remove any tissue debris, blood clot, and any other foreign bodies, the bed was dried with cellulose acetate sponge. Freshly prepared fibrin glue solution (TISSEEL Fibrin Sealant; Baxter AG, Vienna, Austria) was uniformly spread at the trephined edges of the recipient bed using the Duploject injector (TISSEEL; Baxter AG, Vienna, Austria), and the donor lenticule was placed over the host bed. A firm and uniform pressure was applied from the center to the periphery and more toward the edge to spread the fibrin glue uniformly beneath the donor lenticule, thereby aiding in the process of adherence of the donor lenticule to the host bed. The firm apposition of the graft to the host bed with a well-apposed graft host junction was ensured with the aid of iOCT. No discrepancy was noted in the graft and host size, and the graft host junction was continuous (Figure 2, E and F).
A bandage contact lens was applied over the graft at the end of the surgery, which was followed by subconjunctival injection of gentamicin (20 mg in 0.5 mL) and dexamethasone (2 mg in 0.5 mL). The host corneal buttons were subjected to histo-pathologic evaluation. The corneal tissue specimen from the host was fixed in formalin, and sections were stained using hematoxylin and eosin stains for light microscopy examination. Special staining (Congo red) was also done to confirm presence of amyloid deposition (Figure 3).
The patient attained a BCVA of 6/9 and 6/12 in the right and left eye, respectively. The graft was clear and well apposed, with minimal interface haze bilaterally. The patient obtained a significant decrease of photophobia and lacrimation post-operatively. After the keratoplasty, the patient was started on daily topical moxifloxacin 0.5% eye drops and topical prednisolone acetate 1.0% eye drops 6 times a day for 48 hours, followed by 4 times a day for 4 weeks. Medications were tapered gradually, with continuation of topical carboxymethylcellulose eye drops 0.5% at 6 times a day. The patient was also started on eye ointment tacrolimus 0.03% twice daily. The patient did not develop any recurrence during the 20-month follow-up period.
Histopathologic evaluation revealed thinned out, irregular, atrophic epithelium with absence of underlying Bowman membrane. There were irregular deposits of extracellular eosinophilic material beneath the epithelium. On Congo red staining, the deposits tested positive and showed apple green birefringence under polarized light, suggesting amyloid deposition (Figure 3).
At 12-month follow-up, the BCVA was main-tained at 6/9 and 6/12 in the right and left eye, respectively. The refractive error was +1.25 diopter sphere/-1.00 diopter cylinder at 160 degrees in the right eye and +0.50 diopter sphere/-1.25 diopter cylinder at 170 degrees in the left eye. The contrast sensitivity improved from 0.3 to 1.35 in the right eye and from 0.15 to 1.2 in the left eye postoperatively. Keratometry was 42.75/43.75 and 42.25/43.5 in the right and left eye, respectively. A clinical examination revealed a clear graft with well-apposed graft host junction (Figure 4). An ASOCT of the right eye revealed a clear interface with well-apposed graft host junction (Figure 5). The graft host thickness on ASOCT demonstrated a sequential decrease in the anterior donor thickness with total corneal/donor thickness varying from 759/327 μm in the early postoperative period to 627/288 μm at the 3-month visit and to 546/258 μm at the 12-month follow-up visit.
Gelatinous drop-like dystrophy is a rare, inherited disorder that causes significant visual disability and morbidity. It typically has a bilateral asymmetrical presentation with subepithelial deposition of amyloid proteins. Depending on the level of involvement, it can be treated with phototherapeutic keratectomy in lesions with superficial corneal involvement or surgically with anterior lamellar to full-thickness penetrating keratoplasty. Management of these cases with sutureless keratoplasty circumvents the need for sutures, increasing patient comfort, decreasing surgical time, and eliminating chances of astigmatism, infection, and recurrence. Although certain studies have evaluated the role of phototherapeutic keratectomy in patients with GDLD with superficial involvement, the outcomes are poor in view of persistent postoperative haze, hyperopic shift, and irregular astigmatism.4 To the best of our knowledge, this is the first time a patient with GDLD has been effectively treated with iOCT-guided automated sutureless ALTK.
Lamellar keratoplasty is a procedure in which the diseased layers of the cornea are selectively replaced by healthy donor tissue. In cases of anterior stromal opacities, anterior lamellar keratoplasty targets the replacement of only the anterior stromal tissue, preserving the endothelium and thereby obviating the risk of endothelial rejection. The technique of selective replacement of a diseased cornea has certain advantages in terms of less intraoperative com-plications, maintaining globe integrity, and lesser chances of graft rejection in the postoperative period as lesser amounts of donor tissue are transplanted compared with that shown with full-thickness penetrating keratoplasty. Full-thickness penetrating keratoplasty is associated with its own set of problems, including risk of immune rejection, weak graft host junction, suture-related complications like loose sutures, suture-related infiltrates, astigmatism, and a longer recovery time. Lamellar keratoplasty is advantageous in cases of GDLD, considering the inevitable recurrence with a full-thickness graft, as the inner corneal layers are essentially normal in patients with GDLD.3 This can also reduce the risk of endothelial rejection reported in a few cases of GDLD.5
The use of iOCT, as shown in our patient, can provide continuous feedback of intraoperative surgical maneuvers. It is useful in guiding lamellar corneal transplant surgeries. The use of iOCT can help to measure central corneal thicknesses of donor and host, both of which are important parameters for deciding the blade size to be used in microkeratome for dissection. In addition, when donor tissue must be manually prepared, iOCT acts as a guiding tool to minimize complications. During the ALTK procedure, proper apposition can be done with the help of iOCT. In DALK procedures, the iOCT guides every step of the surgery starting from depth of trephination to graft host apposition. In manual DALK, iOCT helps in identifying a thinner location so that extra precaution can be taken while maneuvering in and around the same area. Any small perforation in DALK can be identified easily, and further steps can be taken to avoid the case getting converted to full-thickness penetrating keratoplasty.6
Suture-related factors account for 14% to 60% of graft infections, compromising graft survival after keratoplasty.7,8 These complications can be avoided with the use of human fibrin glue in what has been described as the sutureless anterior lamellar keratoplasty. In GDLD, recurrence of corneal lesions after keratoplasty has been shown to occur along the sutures.5 In addition, sutures may induce localized new vessels, further potentiating inflammatory mediators in these cases. The use of fibrin glue as a substitute to corneal sutures addresses the above concerns. It has the additional advantage of allowing sufficient working time before “setting,” possesses adequate tensile strength to maintain corneal integrity, does not induce inflammation, permits clear vision, and promotes healing at the interface.
The fibrin-aprotinin tissue adhesive is available in 2 vials. One contains fibronectin, fibrinogen, factor XIII, and aprotinin (an antifibrinolytic agent), whereas the other contains thrombin and calcium chloride. Rapid coagulation shortens the time needed to hold the graft in place and minimizes chances of slippage.
The brevity and expedience of the procedure, increased patient comfort because of lack of sutures, minimal disturbance of the visual axis, and good long-term results with no complications make the sutureless lamellar corneal graft a quick, safe, stable, long-lasting, and efficient treatment modality and a viable alternative to a full-thickness penetrating graft in these cases. This report, thus, highlights the safety and efficacy of use of tissue adhesives as a substitute to sutures in lamellar keratoplasty in patients with GDLD.
DOI : 10.6002/ect.2019.0043
From the 1Cornea, Cataract, and Refractive Surgery Services and
Pathology Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All
India Institute of Medical Sciences, New Delhi, India
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Noopur Gupta, Room no. S-2, First floor, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India
Phone: +91 11 26594004
Figure 1. Clinical Photograph of the Left Eye
Figure 2. Clinical Photograph of the Right Eye
Figure 3. Histopathologic Examination
Figure 4. Clinical Photograph of the Right Eye 12 Months Postoperatively Revealing a Clear Graft, Well-Apposed Graft Host Junction, and Lack of Any Interface Haze (×16 magnification)
Figure 5. Postoperative Anterior Segment Optical Coherence Tomography of the Right Eye