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Purpose: To assess the efficacy and safety of human leukocyte antigen-matched allogeneic cultivated limbal epithelial stem cell grafts in the treatment of aniridia-associated keratopathy (AAK). Methods: Six eyes of 6 patients with severe AAK received an allogeneic stem cell graft between January 2010 and March 2017. Anatomical and functional results were assessed at 6 months, 1 year, 2 years, and the final follow-up visit available. Safety analysis was performed by considering all perioperative and postoperative adverse events and additional surgeries required during the follow-up period. Results: The mean follow-up was 53.6 months (range 24-104 months). In most patients (80%), there was an early improvement of the keratopathy postoperatively, which slowly regressed during longer follow-up. At the final follow-up, 4 of the eyes were graded as failure and 1 eye was graded as partial success. Grading the sixth eye was not possible because of an adverse event. None of the patients maintained a total anatomical success in the long-term. Only 1 patient maintained a modest improvement in best-corrected visual acuity from hand motion to counting fingers. Four serious adverse events were recorded in 2 patients. Conclusions: Severe AAK remains a challenging condition to manage. Transplantation of allogenic ex vivo cultivated limbal stem cells may provide a temporary improvement in ocular surface stability, but anatomical and functional results are poor in the long-term. The eyes are prone to adverse events, and any surgical treatment should take this into consideration.

PURPOSE Panel-reactive antibody (PRA) testing has been widely adopted in solid organ transplantation for risk assessment in potential allograft recipients but has not been studied in the context of ophthalmic transplantation. The purpose of this study is to evaluate outcomes in patients undergoing ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) relative to preoperative PRA level. METHODS This is retrospective chart review of all eyes with documented PRA level that underwent OSST for LSCD between May 2000 and March 2019 at a single institution. Eyes with stable ocular surface but

PURPOSE To evaluate the outcomes of Descemet membrane endothelial keratoplasty (DMEK) in aphakic and aniridic eyes. METHODS A retrospective chart review of either aphakic or aniridic patients who underwent DMEK at Toronto Western Hospital, Canada, between 2015 and 2019 was performed. Demographic characteristics, intraoperative and postoperative complications, and best corrected visual acuity (BCVA) were analyzed. RESULTS Nine eyes of 9 patients, aged 51.0 ± 8.6 years, were included (3 aniridic, 5 aphakic, and 1 combined). The average follow-up was 15.7 ± 12.7 months. The best corrected visual acuities before surgery and 3 and 6 months after surgery were 1.28 ± 0.47, 1.33 ± 0.98, and 1.03 ± 0.56 LogMAR, respectively. Six eyes (67%) had graft detachment, with 3 of them larger than 30% of the graft area. One eye (11%) developed hyphema. The overall failure rate was 88% (8 of 9 eyes), meaning only one was viable at the last follow-up. Primary graft failure was seen in 4 eyes (44%) after detachment (n = 3) and intraoperative hyphema (n = 1). Secondary failure occurred in 4 eyes (44%) at 7, 12, 15, and 36 months. The secondary failure at 36 months was after rejection. Failures were managed with penetrating keratoplasty (n = 2), repeat DMEK (n = 3), Descemet stripping automated endothelial keratoplasty (n = 1), and observation because of poor vision potential (n = 2). Cumulative graft survival probabilities at 12 and 24 months were 44% and 17%, respectively. CONCLUSIONS Aniridic and aphakic patients experienced unacceptably high detachment and failure rates after DMEK. Before performing DMEK, the risks and benefits should be carefully weighed and perhaps other keratoplasty techniques should be used.

The purpose of this study was to evaluate the feasibility of treating aniridia-associated keratopathy with a nonpenetrating artificial cornea in 2 patients with corneal blindness secondary to aniridia.This was a prospective, nonrandomized, interventional study of 2 consecutive patients with corneal blindness caused by aniridia. Ophthalmological examination was performed before the nonpenetrating keratoprosthesis surgery and then repeated 1, 7, 15, 30, 90, and 180 days and subsequently every 90 days thereafter. Optical coherence tomography was performed 90 days postsurgery to assess the position of the implant.Visual acuity improved significantly after the KeraKlear surgery. Postoperative findings included periprosthetic corneal thinning, neovascularization, and retroprosthetic opacity.KeraKlear nonpenetrating artificial corneas represent a promising alternative to keratolimbal allografts and Boston keratoprosthesis for the treatment of aniridia-associated keratopathy.

Purpose To evaluate the utility, safety, and efficacy of a parallel or cloverleaf retention suture in Descemet stripping automated endothelial keratoplasty that does not penetrate donor tissue and can be removed at the slit lamp for patients at high risk of graft detachment. Methods Data were prospectively collected over 9 years from patients who received a retention suture. Indications for use of a retention suture included difficulty with postoperative positioning, abnormal intraocular anatomy including glaucoma tube shunts, trabeculectomies, anterior chamber intraocular lens implants, previous vitrectomy, aniridia, and aphakia, or history of previous graft detachment. Results Of 128 surgeries, 12 (9.4%) required additional intervention for graft reattachment (rebubble). Overall, 120 grafts (93.8%) remained clear and attached either after surgery with a retention suture or after rebubble procedures. Mean endothelial cell density at 1 year was 1840 cells/mm, and mean endothelial cell density loss was 37.3%. Conclusions A cloverleaf or parallel retention suture in conjunction with Descemet stripping automated endothelial keratoplasty seems to reduce the risk of detachment in high-risk patients, while maintaining adequate cell density and graft clarity at 1 year.

PURPOSE To report the intermediate- and long-term visual outcomes and complications with the Boston type 1 keratoprosthesis (KPro) for the management of aniridic keratopathy. METHODS A retrospective chart review of 46 eyes of 34 patients (20 females and 14 males) with aniridic keratopathy who underwent Boston type 1 KPro surgery by a single surgeon from 2004 to 2012 with minimum 2-year follow-up was conducted. Preoperative, intraoperative, and postoperative parameters were collected and analyzed. The primary outcome was the change in best-corrected visual acuity. Secondary outcomes included the rate of retroprosthetic membrane formation, glaucoma progression, glaucoma tube revisions, and KPro retention. RESULTS Mean age of the patients was 43.5 ± 19.8 years with a mean follow-up period of 4.5 ± 1.6 years (range 2-7.4 years). Thirty-four eyes (74%) had previously failed keratoplasty. Thirty-five eyes (76%) previously underwent ocular surface stem cell transplantation, specifically a keratolimbal allograft. Within the first 6 months postoperatively, 74% (34/46) of patients experienced a gain of ≥2 lines of vision. Overall, there was a gain of ≥2 lines of vision in 43.5% (20/46) of patients at last follow-up. The rate of retroprosthetic membrane formation was 61%, the rate of glaucoma onset/progression was 26%, the rate of tube revision was 31%, and the KPro retention rate was 87%. CONCLUSIONS This study confirms that initial visual improvement in aniridic keratopathy cases occurs at a high rate with the Boston type 1 KPro but also found progressive loss of these initial visual improvements.

PURPOSE To report the short-term visual outcomes and complications of keratoprosthesis surgery as the primary penetrating corneal procedure for patients at high risk for conventional corneal transplantation. METHODS A retrospective chart review was conducted of 21 eyes of 19 patients who underwent either Boston keratoprosthesis type I or type II as the primary penetrating corneal procedure from February 2007 to March 2011. RESULTS Nineteen type I (90.5%) and 2 type II (9.5%) Boston keratoprosthesis procedures were performed in 19 patients. Mean follow-up was 14.6 months (range, 6-36.3 mo). Primary indications for surgery included chemical or thermal injury, aniridia, and Stevens-Johnson syndrome. Preoperative best-corrected visual acuity (BCVA) ranged from 20/100 to light perception and was count fingers or worse in 20 eyes (95.2%). At last follow-up for all eyes, 15 eyes (71.4%) achieved BCVA≥20/200 and 4 eyes (19%) improved to BCVA≥20/50. No intraoperative complications occurred. Postoperative complications include retroprosthetic membrane formation (47.6%), cystoid macular edema (33.3%), elevated intraocular pressure (23.8%), glaucoma progression (14.3%), and endophthalmitis (4.8%). The initial keratoprosthesis was retained in 19 eyes (90.5%). CONCLUSION The Boston keratoprosthesis, based on early follow-up, is a good alternative as a primary penetrating corneal procedure in a select group of patients with very poor prognosis for penetrating keratoplasty. Although complications can occur and require close monitoring, visual acuity significantly improved in the majority of patients.

As our understanding of phenotype has improved with improving anterior segment imaging, it has become increasingly clear that the early genotype-phenotype correlations were largely misled by inaccurate phenotyping. Using a novel classification, congenital or neonatal corneal opacification can be considered to be primary or secondary. Secondary corneal disease may be developmental or acquired. Genetic analysis using this phenotypic classification becomes easier to navigate. Primary corneal disease includes endothelial dystrophies, corneal dermoids, cornea plana, and CYP1B1 cytopathy. Genotyping for all these conditions is reasonably advanced. Secondary developmental corneal disease includes entities that are the least well understood genotypically. These are kerato-irido-lenticular dysgenesis (also known as Peters anomaly, types 1 and 2). The genotyping literature of these conditions is littered with confusion. Iridocorneal adhesions (Peters anomaly 1) are often avascular, whereas keratolenticular adhesions (Peters anomaly 2) are usually vascularized. Children with a known molecular diagnosis can have iridocorneal adhesion in one eye and keratolenticular adhesion in the other eye. This further supports the notion that Peters anomaly 1 or 2 is a sign and not a diagnosis. Further types of kerato-irido-lenticular dysgenesis are those in which the lens fails to form or forms and then degenerates. Genotyping in these cases has been somewhat more fruitful but, as always, not comprehensive. If the lens fails to form or forms partially, the gene involved is FOXE3, which is a lens gene. Not surprisingly, if the lens forms partially or fails to form, this has an effect on the vitreous and the drainage angle. These cases are often associated with severe glaucoma. Other secondary developmental corneal diseases may include Axenfeld-Rieger syndrome, Aniridia, and primary congenital glaucoma, all of which have specific genotypic characterization. Other secondary causes are acquired and include infection, trauma, and metabolic disorders.

Purpose. Successful limbal allotransplantation allows regression of limbal stem cell deficiency features. Transplant survival is presumed if clinical improvement occurs. However, positive proof of surviving transplanted stem cells remains difficult. This follow-up study attempted to prove donor cell survival 5 years after limbal stem cell allograft in one woman with aniridia. Methods. Impression cytology and single-cell DNA fingerprinting were used to investigate a previously studied patient. Corneal epithelial cells were harvested from five sites and isolated by micromanipulation. Polymerase chain reaction and short tandem repeat profiling were used to obtain forensic standard "DNA fingerprints" from single cells. (The technique is described in the preceding article, Part I.) Blood samples yielded host and donor DNA for comparison. Negative controls were performed for impression cytology and polymerase chain reaction. Simultaneous micro-scrape samples were also taken. Results. Impression cytology samples permitted informative DNA fingerprints from all corneal sites and represented 76% (23/30) of tested cells. Fifty percent (15/30) of the fingerprints were "specific" but 83% (19/23) matched the host DNA fingerprint. The remaining 17% (4/23) represented contamination from various sources. Specific fingerprints were obtained in 55% (10/18) of the cells from micro-scrape samples. All samples giving sufficient information matched the host DNA fingerprint. All tested blood samples gave specific fingerprints. None of the sampled corneal cells gave a donor DNA fingerprint. Conclusions. In a single patient, no detectable long-term donor cell survival exists at 5 years. Positive identification would have provided unequivocal proof of donor cell survival. This technique gives useful information even if contamination occurs.

PURPOSE Using staining pigments with which we had gained experience in dermatography (medical tattooing) treatments of leucoma corneae, a new approach was developed to create an artificial iris-like staining at the mid-stromal level of the cornea to treat photophobia in a patient with posttraumatic aniridia. METHODS After a central 4-mm half-depth trephination, a lamellar dissection of the corneal stroma toward the limbus was performed. A combination of colored pigments was introduced into this midstromal space, until a light blue artificial iris (to match the contralateral eye) with adequate blocking of light was created. RESULTS A stable artificial iris was created in the mid-stromal level of the cornea. CONCLUSION Dermatography pigments are stable in the corneal stroma and are useful to treat photophobia in aniridia following trauma.

PURPOSE: Defects in the iris are associated with clinically significant optical anomalies, such as glare and peripheral light scatter; however, current artificial-iris technology remains inadequate. The purpose of this study was to explore the practicality of a lamellar intrastromal tattoo technique as a treatment modality to correct optical and cosmetic defects resulting from simulated iris abnormalities in eye-bank eyes. METHODS: Simulated iris defects (abnormally large pupil, sector iridectomy, iridodialysis, and aniridia) were produced in a series of eye-bank eyes. Depending on the simulated iris defect, one or two lamellar channel(s) were created at 50% depth of the cornea via a peripheral incision (1.8 mm) with specialized proprietary instruments (KeraVision, Inc., Fremont, CA, U.S.A.). Commercially available tattoo pigment was inserted through the lamellar channel(s) and blended into the defective region of the iris. RESULTS: The tattoo treatment was relatively simple to perform. Tattoo pigment was inserted uniformly through the small incision, and adequate color blending to match the recipient iris was achieved. The intrastromal tattoo effectively obscured light. CONCLUSION: The lamellar intrastromal tattoo technique appeared to be efficacious for treating different types of iris defects in eye-bank eyes. Further investigation of this technique in nonsighted patient eyes is warranted.

Purpose To describe the incidence and prevalence of glaucoma in a patient population with severe ocular surface disease (OSD). Methods A retrospective case series was compiled from all charts of patients in the Cincinnati Eye Institute/University of Cincinnati and University of Minnesota population with a diagnosis of severe OSD from 1991 to 2003. The incidence and prevalence of glaucoma in the overall patient population were identified, and stratified into disease subgroups. Results Of the 108 eyes evaluated in this study, 71 were diagnosed with glaucoma. The overall prevalence of glaucoma in patients with severe OSD is 65.7%, with a range from 42.9% to 88.4%. Analysis by subgroup shows the highest percentage of patients with concurrent glaucoma fall into the categories of aniridia and chemical injury, and the lowest was noted in those patients with autoimmune or iatrogenic OSD. Overall, the incidence of glaucoma was 20.4%, with a range of 13.6% to 60%. Conclusions Compared with previous studies, our results show a significantly higher prevalence of glaucoma in patients with severe OSD. This information warrants increased attention to treatment and management of OSD and concurrent glaucoma.

Purpose: To present an aniridic patient with failed penetrating keratoplasties OU (PK) who underwent successful repeat PK OD, which has remained clear for 4 years with continuous bandage lens (BCL) wear. Methods: A 73-year-old aniridic woman who had a failed PK complicated by ocular surface disease refused limbal stem cell transplantation and underwent repeat PK in her right eye. The immediate postoperative course was uneventful except for mild irregularity of the graft epithelium. Two months postoperatively, she presented with an epithelial defect along the inferotemporal graft margin adjacent to an exposed, loose interrupted suture. The suture was removed, and although the initial epithelial defect healed, she suffered recurrent episodes of epithelial breakdown and generalized whorl epitheliopathy. A BCL was inserted and rendered prompt healing of the graft epithelium, which has remained smooth and intact for 4 years. Results: The graft remains thin and clear with a smooth and intact epithelial surface beneath the BCL and no signs of limbal stem-cell deficiency. Conclusion: Long-term BCL wear provided good corneal transplant surface protection in an aniridic patient with recurrent epithelial breakdown, thereby sparing the need for limbal stem cell transplantation and the use of potentially toxic systemic immunosuppressive therapy. Meticulous follow-up is required to monitor contact lens loss and epithelial breakdown as well as signs of secondary infectious keratitis.

PURPOSE To report the outcomes of Boston keratoprosthesis (K-pro) type I implantation for congenital aniridia. METHODS A retrospective review of the medical records of every patient with congenital aniridia who underwent Boston K-pro type I implantation at the University of Iowa Hospitals and Clinics from January 1, 2009, through December 31, 2011 was performed. The main outcome measures were visual acuity, graft retention, and postoperative complications. RESULTS A total of 7 eyes (7 patients) met the inclusion criteria. The mean patient age was 52 years (range, 12-85 years). The preoperative visual acuity was 20/1600 in 6 eyes (85.7%) and hand motions in 1 eye (14.3%). After a median follow-up period of 18 months (range, 3-30 months), the median final best spectacle-corrected visual acuity was 20/200 (range, 20/100 to light perception). This included 2 eyes (28.6%) that were 20/100 and 5 eyes (71.4%) that were better than 20/300. Compared with the preoperative best spectacle-corrected visual acuity, the final vision was improved in 6 eyes (85.7%) and worse in 1 eye (14.3%). The K-pro graft was retained in all 7 eyes (100%). The most common complication was the formation of a retroprosthetic membrane in 3 eyes (42.9%), none of which required either a YAG capsulotomy or a vitrectomy. One eye (14.3%) developed a wound dehiscence that required surgical repair. CONCLUSIONS The Boston K-pro type I is a good option for the visual rehabilitation of eyes with congenital aniridia.

PURPOSE To describe the clinical features of a familial abnormality of the corneal stem cells and to investigate the role of PAX6 mutations in the affected family members. METHODS A family with multiple generations of peripheral keratopathy was evaluated. Because of the corneal phenotypic similarity to aniridia-related keratopathy, it was hypothesized that the affected patients might have a dominantly inherited mutation of PAX6 on chromosome 11. Commercial sequencing of germline DNA from 1 affected family member did not identify any PAX6 mutations in the exons or intron-exon boundary regions. Because the commercial analysis is not designed to identify PAX6 deletions, germline DNA was collected from 5 unaffected and 2 additional affected family members. DNA repeat markers in the region of PAX6 were analyzed to determine whether this chromosomal region segregates with the disease phenotype. RESULTS Affected family members with this autosomal dominant peripheral corneal abnormality showed evidence of progressive corneal stem cell dysfunction. Several individuals demonstrated corectopia, and 1 individual had ectropion uvea but no other iris or ocular abnormalities associated with aniridia. Genotyping data of affected and unaffected family members demonstrated that the PAX6 region does not segregate with the disease phenotype. CONCLUSIONS The features of this autosomal dominant abnormality show some similarity to aniridia, although the classic characteristics of severe iris hypoplasia and macular hypoplasia are absent. Mutational screening and genotyping could not conclusively clarify a role for PAX6 in this disease phenotype, suggesting that it is a distinct clinical and genetic disease entity, not a variant of aniridia.

PURPOSE To describe the variations in intraoperative technique, postoperative complications, and visual outcomes associated with Descemet stripping endothelial keratoplasty (DSEK) after Ophtec iris reconstruction lens implantation. DESIGN Retrospective, interventional, consecutive case series. PARTICIPANTS Patients who underwent DSEK after Ophtec 311 iris reconstruction lens implantation at the Jules Stein Eye Institute, University of California, Los Angeles. METHODS Medical records were reviewed for demographic information, ophthalmic history, DSEK surgical technique, and postoperative clinical course. MAIN OUTCOME MEASURES Intraoperative and postoperative complications and visual outcomes. RESULTS Four patients were identified (1 man and 3 women, age: 43-78). Three of the eyes had undergone prior penetrating keratoplasty (PKP), and each of the eyes had a history of glaucoma, with previous glaucoma surgery having been performed in 2 of the eyes. No intraoperative complications were encountered during the procedures, although an unplanned anterior vitrectomy was required in a previously vitrectomized eye. In each case, a complete air fill of the globe was obtained to ensure adherence of the donor button, and in 3 of the 4 cases, the donor button was sutured to the recipient cornea to prevent potential posterior dislocation. None of the cases developed donor button dislocation or primary graft failure. Corrected distance visual acuities improved to 20/40-20/160, corresponding to a mean improvement of 0.25 (range, 0.12-0.40), limited by irregular corneal astigmatism and advanced glaucomatous optic neuropathy. During a mean follow-up period of 15.6 months (range, 4.9-24.8 months), graft rejection developed in 2 of the 3 eyes with a history of endothelial rejection after PKP (0.42 episode per eye-year). Both of these eyes developed secondary graft failure, which also developed 14 months after DSEK in the other eye with a history of PKP failure before DSEK. CONCLUSIONS DSEK can be successfully performed in eyes with partial or complete aniridia, such as those after Ophtec iris reconstruction lens implantation. Modifications to the standard DSEK technique increase the probability of successful donor adherence and decrease the risk of posterior dislocation of the donor corneal button. However, endothelial rejection may occur at an increased frequency, resulting in secondary graft failure.

PURPOSE:: The purpose of this research is 2-fold. First of all, the level of keratopathy development in patients with congenital aniridia is studied. In addition, a correlation between the effects of ocular surgery on the severity of keratopathy is made. METHODS:: A thorough search for the total number of patients with aniridia in Sweden and Norway was performed. One hundred eighty-one patients were identified and 124 (69%) of these were examined. Three artificial eyes, 16 eyes with corneal transplants, and 1 eye with a corneal limbal allograft were excluded from the study. All participating patients underwent clinical ophthalmologic examinations, including photographs, and their medical history was recorded. A slit lamp was used to examine the presence of keratopathy. RESULTS:: Visible keratopathy was found in 80% of the eyes. Keratopathy that caused impaired visual acuity was found in 26% of the eyes. The study displayed a significant correlation between the level of keratopathy and the patient's age. A significant correlation between the level of keratopathy and intraocular surgery exists. This is irrespective of the patient's age. The study also found that irrespective of the patient's age, a significant correlation between the level of keratopathy and impaired corneal sensitivity exists. CONCLUSIONS:: This research identified the presence of visible keratopathy in 80% of eyes. In addition, 26% of eyes had a keratopathy level that caused visual disturbances. The study showed that the prevalence and severity of keratopathy increased with the patient's age. Further conclusions are that intraocular surgery increases the severity of keratopathy and that the severity of keratopathy is correlated to reduced corneal sensitivity. Finally, extreme care should be taken when selecting patients for intraocular surgery because this procedure can trigger the development of keratopathy. (Less)

Purpose. Encephalocraniocutaneous lipomatosis is a congenital neurocutaneous syndrome characterized by lipomatous craniofa- cial hamartomas. The most common ocular manifestation is epi- bulbar choristoma, but many additional eye anomalies may be present. Methods. To our knowledge, this is the first reported case with bilateral aniridia. We report a case of a boy affected by this syndrome and review the literature. Conclusion. Regarding this case, we suggest adding aniridia to the possible ocular anomalies in this syndrome. Echocardiogram, renal ultrasound, cervical spine x-ray, and elec- troencephalogram (EEG) were normal. Brain computed tomogra- phy showed a fatty growth in the cerebellopontine cistern near the cranial nerve VII-VIII complex, with no pressure on the brainstem. Due to the epibulbar choristomas and preauricular tags, he was first diagnosed with Goldenhar's syndrome, but there were no vertebral or cardiovascular anomalies to support this diagnosis. At the age of 3 weeks, he underwent excision of the epibulbar dermoid and deep anterior lamellar keratoplasty in the left eye. Due to recurrent transplant failures, multiple additional full- thickness keratoplasties were subsequently performed. Cataract, glaucoma, and exotropia developed in this eye; therefore, cataract extraction and posterior chamber intraocular lens implantation were performed at 2 months of age. At 4 weeks of age, he underwent a successful excision of the epibulbar dermoid and deep anterior lamellar keratoplasty in the right eye. Histopathologic examination of the lesion removed from the left eye showed lacrimal gland, cartilage, and adipose tissue covered by nonkeratinized, stratified squamous epithelium, consistent with epibulbar dermoid. At the age of 6 months, his motor development was markedly delayed. He could not roll over, sit, or lift his head. His left arm was paralyzed, and there were pyramidal signs in all four limbs. There were no epileptic attacks, and the EEG was normal. Mag- netic resonance imaging showed bilateral acoustic meatus lipomas in the cerebellopontine angle area, a 45-mm long lipoma anterior to the brainstem from the foramen magnum and along the cervical vertebrae, with pressure on the spinal cord, and three additional lower intraspinal lipomas. No brain or intraorbital anomalies were noted. At this stage, partial excision of the intramedullary lipoma was performed. In addition, a ventriculoperitoneal shunt was in- serted but was subsequently removed due to shunt infection. There was rapid, considerable improvement in the child's motor devel- opment after these procedures. At the age of 2 years, the child is slightly developmentally delayed. He has a functional right eye with a clear graft, aniridia, and coloboma of the retina in this eye and exotropia and glaucoma in the left eye. The left eye corneal graft is edematous. He walks freely, and his language skills are appropriate for his age.

To review the ocular surface and anterior segment findings in Brachmann-de Lange syndrome and describe a new case involving aniridia and congenital glaucoma.A newborn presented 2 days after birth with bilateral cloudy corneas, photophobia, and epiphora. We provide a 5-year descriptive history and clinical course with review of the literature on Brachmann-de Lange syndrome.Multiple ocular surgeries were performed for ocular sequelae from aniridia and congenital glaucoma including Ahmed valve placement and penetrating keratoplasties in both eyes. At 5.5 years of age, the child had a clear graft OD and amblyopia from graft failure OS following recurrent graft infections. A review of Brachmann-de Lange syndrome found 43 patients with ocular surface and anterior segment findings. The most common findings included conjunctivitis, blepharitis, microcornea, and corectopia. Aniridia and congenital glaucoma were not previously reported with Brachmann-de Lange syndrome.Ocular surface and anterior segment abnormalities must be considered when examining patients with Brachmann-de Lange syndrome. Ocular findings may include vision-threatening anomalies, as in our case with aniridia and congenital glaucoma. To our knowledge, these findings are previously unreported in Brachmann-de Lange syndrome.

Using staining pigments with which we had gained experience in dermatography (medical tattooing) treatments of leucoma corneae, a new approach was developed to create an artificial iris-like staining at the mid-stromal level of the cornea to treat photophobia in a patient with posttraumatic aniridia.After a central 4-mm half-depth trephination, a lamellar dissection of the corneal stroma toward the limbus was performed. A combination of colored pigments was introduced into this midstromal space, until a light blue artificial iris (to match the contralateral eye) with adequate blocking of light was created.A stable artificial iris was created in the mid-stromal level of the cornea.Dermatography pigments are stable in the corneal stroma and are useful to treat photophobia in aniridia following trauma.

Corneal lesions in aniridia include peripheral pannus and epithelial abnormalities that may advance centrally, resulting in the need for penetrating keratoplasty. Three patients with aniridia who underwent repeated corneal surgical procedures (one keratectomy and six penetrating keratoplasties) are described herein. A clinicopathological correlation was performed. In all three patients there was evidence of recurrent pannus and epitheliopathy on histopathological examination, which correlates with the clinical findings. These findings suggest that the pathophysiology of recurrent aniridia keratopathy may be related to a primary abnormality in the stem cells of the recipient corneal limbus. Aniridic pannus and epitheliopathy recur in grafts after penetrating keratoplasty and threaten the transplanted cornea. The risk of recurrent keratopathy should be considered when recommending a surgical procedure to patients with aniridia.

Frozen sections of corneoscleral buttons from normal and aniridic donors were stained with hematoxylin and periodic acid-Schiff, monoclonal antibodies AE-5 and AK-2 (to cornea-specific K3 and K12 keratins, respectively), and AM-3 (to conjunctival goblet cells) as well as with subtype-specific antibodies to seven different protein kinase C (PKC) subtypes, the signal transduction isoenzymes increasingly implicated in the regulation of cell growth and differentiation. Compared with the normal cornea, the aniridic cornea showed decreased AE-5 and AK-2 stainings, increased AM-3 staining, attenuated Bowman's membrane, invasion of new blood vessels, and limbal epithelial hyperplasia. In the normal tissue, the corneal epithelium expressed PKC alpha, lambda, and zeta; the limbal and conjunctival epithelia expressed additional PKC gamma. Conjunctival goblet cells expressed only PKC lambda. Within a given epithelium, different PKC subtypes had different cell-layer distributions. In the aniridic tissue, some of the four normally expressed subtypes were expressed in different cell layers, especially at the limbal region. PKC beta and PKC delta, which were normally weakly expressed, were markedly up-regulated. These results support the conclusion that the aniridic cornea does indeed manifest features of limbal stem cell deficiency with decreased corneal epithelial phenotype and increased conjunctival epithelial phenotype. Different capacities of proliferation and differentiation may be affected by the differential expression of PKC subtypes by different cell layers of normal ocular surface epithelia. The aberrant expression of PKC subtypes in aniridia may thus result in abnormal proliferation and differentiation noted in its ocular surface epithelia. Because limbal stem cells are the ultimate source of corneal proliferation and differentiation, we postulate that limbal deficiency in aniridia is a result of abnormal limbal stem cells.

PURPOSE This study aims to evaluate the results of lamellar keratoplasty (LKP) for optical (nontectonic) indications over the past 19 years at our institution, noting the advantages and pitfalls of the procedure. METHODS The study is a retrospective review of 52 central LKPs in 37 patients. Snellen visual acuity, preoperative clinical indications, and postoperative status of the cornea (donor graft, graft-host interface, and recipient cornea) were assessed. RESULTS Postoperative follow-up ranged from 3 months to 18 years (median, 3 years). In descending order of frequency, corneal dystrophies, aniridic keratopathy, corneal scars, and keratoconus were the most common indications for surgery. After surgery, 38% of the eyes were able to achieve 20/50 or better visual acuity. The two most common causes of poor visual acuity were (1) opacification and/or blood vessel growth in the graft-host interface or on the graft surface and (2) high astigmatism. Persistent epithelial defects occurred in 21% of the eyes after LKP. CONCLUSION Although LKP provides a safer alternative to penetrating keratoplasty, it is limited by vision-reducing graft-host interface problems, astigmatism, and difficult surgical technique. We postulate that the current results of LKP may be improved by (1) removing as much recipient corneal stroma as possible (e.g., dissecting down to Descemet's membrane) or, alternatively, using an automated microkeratome and (2) raising the currently used qualitative eyebank standards for accepting LKP donor tissue.

Corneal lesions in aniridia include peripheral pannus and epithelial abnormalities that may advance centrally, resulting in the need for penetrating keratoplasty. Three patients with aniridia who underwent repeated corneal surgical procedures (one keratectomy and six penetrating keratoplasties) are described herein. A clinicopathological correlation was performed. In all three patients there was evidence of recurrent pannus and epitheliopathy on histopathological examination, which correlates with the clinical findings. These findings suggest that the pathophysiology of recurrent aniridia keratopathy may be related to a primary abnormality in the stem cells of the recipient corneal limbus. Aniridic pannus and epitheliopathy recur in grafts after penetrating keratoplasty and threaten the transplanted cornea. The risk of recurrent keratopathy should be considered when recommending a surgical procedure to patients with aniridia.

Aniridia and the iridocorneal endothelial (ICE) syndromes both are conditions which include abnormalities of the cornea, iris, and progressive iridocorneal adhesions which may result in glaucoma. In order to investigate the similarities between aniridia and the ICE syndromes, we performed specular microscopy of the corneal endothelium in nine patients with aniridia. Morphology and density of the corneal endothelium appeared normal for age. We found no evidence of the beaten metal appearance classically seen on specular microscopy in patients with ICE symptoms. This study did not support either an anatomic or pathogenic relationship between aniridia and the ICE syndromes.