Karim Mohamed-Noriega

Early Corneal Nerve Damage and Recovery Following Small Incision Lenticule Extraction (SMILE) and Laser In Situ Keratomileusis (LASIK)

PURPOSE We compared early corneal nerve changes after small incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK). METHODS A total of 12 rabbits underwent LASIK in one eye and SMILE in the fellow eye. Baseline and follow-up evaluations at 1, 2, and 4 weeks postoperatively were performed with in vivo confocal microscopy to evaluate 5 different areas within the treated zone: center, superior, inferior, nasal, and temporal. Cryosections of the corneas and whole mount of the extracted SMILE lenticules were analyzed with immunostaining of βIII-tubulin. RESULTS One week after SMILE and LASIK, a decrease in nerve length and density was observed in all evaluated areas. A trend toward greater subbasal nerve length and density (SLD), more eyes with subbasal nerves (ESN), more eyes with subbasal nerves longer than 200 μm (SNL), and higher mean number of subbasal nerves by frame (NSN) in SMILE than in LASIK groups was observed at subsequent follow-up time points. Only the SMILE group showed a recovery of SLD, ESN, and NSN by week 4 (P > 0.05). A trend toward more eyes with sprouting subbasal nerves and greater mean number of sprouting nerves was observed in LASIK than in SMILE, indicating that more subbasal nerves were disrupted and undergoing regeneration after LASIK. Immunostaining at postoperative week 4 revealed a faster stromal nerve recovery in post-SMILE eyes compared to post-LASIK eyes. CONCLUSIONS Our findings suggest that SMILE results in less nerve damage and faster nerve recovery than LASIK.

Corneal Melting after Collagen Cross-Linking for Keratoconus in a Thin Cornea of a Diabetic Patient Treated with Topical Nepafenac: A Case Report with a Literature Review

Purpose: To report the case of a 50-year-old woman with diabetes that presented with corneal melting and perforation 6 weeks after collagen cross-linking (CxL) for keratoconus (KC) and postoperative use of nepafenac eye drops, a nonsteroidal anti-inflammatory drug (NSAID). Methods: This is a case report of a patient with diabetes, KC and a thin cornea that had undergone left eye corneal CxL at a different hospital followed by postoperative use of nepafenac eye drops for 6 weeks. Results: The patient presented for the first time to our clinic with left corneal melting, perforation and iris prolapse 6 weeks after corneal CxL and topical nepafenac use. She was treated with a left eye tectonic penetrating keratoplasty, extracapsular cataract extraction, intraocular lens implantation and pupilloplasty. Conclusions: The corneal melting and perforation in this patient was associated with multiple risk factors: (1) nepafenac eye drop use, (2) CxL in a cornea thinner than 400 µm and (3) diabetes. The recommended corneal thickness limits should be respected. Topical NSAIDs should be used with caution if used as postoperative treatment after corneal CxL and in patients with diabetes, epithelial defect or delayed healing, because of the possible increased risk for corneal melting when multiple risk factors are observed.

Corneal transplantation: changing techniques.

We read with interest the article by Larkin et al. “Centre-specific variation in corneal transplant outcomes in the United Kingdom,” which was published in February 2011 (1). However, we felt that there were a few points that need clarification. The authors report that graft survival rates for corneal transplantation were not significantly different between those performed by highand low-volume centers (more than 50 and less than 10 procedures, respectively) and between highand low-volume surgeons (more than 30 and less than 10 procedures, respectively) at 5 years in patients with the diagnosis of keratoconus, Fuch’s endothelial disease, or pseudophakic corneal edema (1). Mean best-corrected visual acuity (BCVA) at 2 years was the same in highvs. low-volume centers or surgeons. However, a larger proportion of patients in high-volume centers or surgeons achieved BCVA of 6/12 or better at 2 years (1). The title of the article indicates a study in corneal transplant outcomes. However, corneal transplantation encompasses many techniques, and in 2011 corneal transplantation is not synonymous with penetrating keratoplasty (PK), the procedure that all the patients underwent in this study. PK is a technique where all layers of the cornea are replaced. However, there are many newer surgical corneal transplantation techniques that are designed to only replace the damaged layer of tissue and retain the unaffected healthy cornea. These techniques are called lamellar keratoplasty (LK) (2, 3). Hence, the title of the article should be “Centre-specific variation in penetrating keratoplasty outcomes in the United Kingdom.” The cornea is a highly organized, transparent tissue with five distinct layers: epithelium, Bowman’s membrane, stroma, Descemet’s membrane (DM), and endothelium (2). This layered structure allows selective replacement of only the diseased cornea a feasible option. LK is divided into two major types: (1) anterior lamellar keratoplasty (ALK) where the anterior part of the cornea is completely or partial replaced by donor allograft tissue while retaining the recipient unaffected DM and endothelium or (2) endothelial keratoplasty (EK) where there is allograft replacement of the diseased DM and endothelium but the recipients stroma is retained (2, 3). Over the past decade, there has been a shift to lamellar procedures by most progressive corneal surgeons. This pattern of shifting in techniques is clearly seen from our audit data at the Singapore National Eye Centre (Fig. 1). From 1991 to 2010, our data show a change in technique which clearly demonstrates a shift away from PK in direction to more selective lamellar procedures. From 2006 to 2010, the shift is more obviously seen mainly because of the emergence of the EK technique. The diagnoses reviewed in the article by Larkin et al., which underwent PK, would now undergo either an EK for Fuch’s endothelial disease/pseudophakic corneal edema or ALK for keratoconus in the majority of cases. Hence, the results in the article are really applicable to surgery per-

Advances and Clinical Applications of Anterior Segment Imaging Techniques

With the rapid development of computer science and technologies in recent years, there has been dramatic advance in anterior segment imaging. As we have mentioned in the call for papers for this special issue, manuscripts are covering the topics of anterior segment imaging techniques including anterior segment optical coherence tomography (OCT), specular microscopy, corneal topography, confocal microscopy, and ultrasound biomi-croscopy (UBM). These techniques have enabled precise visualization and objective assessments of anterior segment structures; thus, these devices have become essential tools for better diagnosis and treatment of anterior segment diseases including corneal disorders, cataract, glaucoma, and even disorders of the lacrimal system. Future development of novel modalities, that is, en face OCT or ultrahigh-resolution OCT, is expected to allow more detailed visualization at a microscopic level, which would provide even more understanding of anterior segment pathology at a cellular level. In this special issue, the authors contributed 15 original articles and 4 review papers regarding technologies of the anterior segment imaging and clinical application of the imaging devices. The authors have contributed the results of their original researches on various topics on anterior segment imaging: (1) agreement between gonioscopic examination and swept source OCT imaging; (2) preliminary outcomes of accelerated corneal collagen cross-linking using topography-guided ultraviolet-A energy emission; (3) anterior segment changes before and following laser peripheral iridotomy of iris bombe in patients with uveitic secondary glaucoma; (4) anterior segment measurements with swept source OCT before and after ab interno trabeculotomy; (5) effects of a new type implantable collamer lens implantation on vision-related daily activities; (6) corneal epithelial remodeling after transepithelial photorefractive keratectomy for myopia; (7) measurement of anterior chamber volume in cataract patients using swept-source OCT; (8) biomechanical findings in contact lens-induced corneal warpage; (9) quantitative analysis of lens nuclear density using OCT with a liquid optics interface; (10) rotating Scheimpflug imaging indices in different grades of keratoconus; (11) evaluation of outflow structures in vivo after the phacocanaloplasty; (12) evaluation of corneal epithelial thickness in asymmetric keratoconic eyes and normal eyes using Fourier domain OCT; (13) central corneal thickness measured using spectral-domain OCT and associations with ocular and systemic parameters; (14) anterior segment changes in pseudophakic eyes after pars plana vitrectomy with silicone oil or gas tamponade using UBM imaging; and (15) UBM comparison of ab interno and ab externo intraocular lens scleral fixation. This special issue also includes review articles on the following topics: (1) application of Scheimpflug …

Confocal microscopy findings in deep anterior lamellar keratoplasty performed after Descemet's stripping automated endothelial keratoplasty.

Background This study describes the in vivo confocal microscopy findings in two patients who had deep anterior lamellar keratoplasty (DALK) following Descemet’s stripping automated endothelial keratoplasty (DSAEK). Methods The study reviewed the cases of two patients who first underwent DSAEK followed by DALK when their vision failed to improve due to residual stromal scarring. In the first case, a DSAEK was performed for a patient with pseudophakic bullous keratopathy. After surgery, the patient’s vision failed to improve satisfactorily due to residual anterior stromal opacity and irregularity. Subsequently, the patient underwent a DALK. The same two consecutive operations were performed for a second patient with keratoconus whose previous penetrating keratoplasty had failed and had secondary graft ectasia. In vivo confocal microscopy was performed 2 months after the DALK surgery in both cases. Results At 3 months after DALK, the best-corrected visual acuity was 6/30 in case 1 and 6/24 in case 2. In vivo confocal microscopy in both cases revealed the presence of quiescent keratocytes in the stroma layers of the DSAEK and DALK grafts, which was similar in the central and peripheral cornea. There was no activated keratocytes or haze noted in the interface between the grafts. Conclusion Our short-term results show that performing a DALK after a DSAEK is an effective way of restoring cornea clarity in patients with residual anterior stromal opacity. In vivo confocal microscopy showed that there were no activated keratocytes seen in the interface of the grafts, which suggests that optimal visual acuity may be obtained with minimal interface haze.

Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea, and retina

Olfactomedin‐like is a family of polyfunctional polymeric glycoproteins. This family has at least four members. One member of this family is OLFML3, which is preferentially expressed in placenta but is also detected in other adult tissues including the liver and heart. However, its orthologous rat gene is expressed in the iris, sclera, trabecular meshwork, retina, and optic nerve.

Expression of growth hormone gene in the baboon eye

&NA; The human growth hormone (GH) locus is comprised by two GH (GH1 and GH2) genes and three chorionic somatomammotropin (CSH1, CSH2 and CSH‐L) genes. While GH1 is expressed in the pituitary gland, the rest are expressed in the placenta. However, GH1 is also expressed in several extrapituitary tissues, including the eye. So to understand the role of this hormone in the eye we used the baboon (Papio hamadryas), that like humans has a multigenic GH locus; we set up to investigate the expression and regulation of GH locus in adult and fetal baboon ocular tissues. We searched in baboon ocular tissues the expression of GH1, GH2, CSH1/2, Pit1 (pituitary transcription factor 1), GHR (growth hormone receptor), GHRH (growth hormone releasing hormone), GHRHR (growth hormone releasing hormone receptor), SST (somatostatin), SSTR1 (somatostatin receptor 1), SSTR2 (somatostatin receptor 2), SSTR3 (somatostatin receptor 3), SSTR4 (somatostatin receptor 4), and SSTR5 (somatostatin receptor 5) mRNA transcripts and derived proteins, by qPCR and immunofluorescence assays, respectively. The transcripts found were characterized by cDNA cloning and sequencing, having found only the one belonging to GH1 gene, mainly in the retina/choroid tissues. Through immunofluorescence assays the presence of GH1 and GHR proteins was confirmed in several retinal cell layers. Among the possible neuroendocrine regulators that may control local GH1 expression are GHRH and SST, since their mRNAs and proteins were found mainly in the retina/choroid tissues, as well as their corresponding receptors (GHRH and SSTR1‐SSTR5). None of the ocular tissues express Pit1, so gene expression of GH1 in baboon eye could be independent of Pit1. We conclude that to understand the regulation of GH in the human eye, the baboon offers a very good experimental model. HighlightsThis is the first report of the presence of GH in the baboon eye.The GH transcript isolated from the baboon eye confirms a new expression site for this hormone.GH and GHR proteins were present not only in retinal ganglion cells (RGC) but also in the entire retina.GH and its GHR were both seen localized in the cytoplasm as well as in the nucleus by immunohistochemistry.GH may trigger both autocrine and paracrine specific action in different retinal cell lines in the baboon.

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon)

BackgroundThe olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon.ObjectiveThe aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology.MethodsOLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays.ResultsOLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human’s orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear.ConclusionsExpression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Deep anterior lamellar keratoplasty: surgical techniques, challenges, and management of intraoperative complications.

Lamellar corneal transplantation allows for targeted replacement of just the diseased corneal layers. Although full-thickness or penetrating keratoplasty (PK) has been the predominant form of corneal transplantation, anterior lamellar keratoplasty (ALK) avoids unnecessary replacement of the healthy endothelium in cases where only the anterior corneal layers are diseased. Thus, ALK is an essentially extraocular procedure that has a reduced risk of endothelial rejection and graft failure; as well as reduced endothelial cell loss. Other advantages include a tectonically stronger eye and a reduced need for long-term topical corticosteroids compared with PK, as endothelial rejection is obviated. As most conditions that affect the anterior cornea such as keratoconus, stromal scars, or corneal dystrophies are in young patients, it is important to consider ALK in these patients due to the longer graft survival and reduced endothelial cell loss. Despite these advantages, PK is still performed more commonly than ALK around the world. This is because ALK [especially deep anterior lamellar keratoplasty (DALK), which often aims to bare Descemet membrane (DM)] may be technically more difficult to perform well. The Eye Bank Association of America reported in 2009 that only 2% of over 55,000 corneal grafts performed in the United States were

Sweating of Descemet's membrane during deep anterior lamellar keratoplasty in absence of perforation.

We report a case of spontaneous Descemet’s membrane sweating of aqueous humor during a manual deep anterior lamellar keratoplasty (DALK) without perforation of Descemet’s membrane. An 81-year-old female developed a neurotrophic central ulcer with descemetocele in the right eye, and her visual acuity was count fingers at 30 cm. She was unresponsive to medical treatment, and an uneventful manual DALK was performed. Six months after surgery, unaided visual acuity improved to 6/30. Seven months after surgery, the patient had a decrease in visual acuity to count fingers in the same eye. She was diagnosed as having corneal melting with a central descemetocele in the previous lamellar graft. A repeat manual DALK graft was performed. Lamellar dissection was performed starting from the edge of descemetocele, proceeding to the corneal periphery and maintaining the surgical plane of the previous DALK. During the surgical procedure, continuous and localized sweating of aqueous through Descemet’s membrane was observed in the area of the descemetocele. After drying of the recipient bed, no visible perforation of Descemet’s membrane was found. After removal of the previous DALK graft, a new stromal lamellar graft was sutured. The surgery was concluded without complications. One day after surgery, the graft was clear, with no detachment of Descemet’s membrane. If Descemet’s membrane sweating is observed during DALK and there is no visible perforation, the reason may be a hidden micron perforation in an intact Descemet’s membrane. It is recommended to continue with surgery maintaining maximum diligence and low intraocular pressure to prevent extension of micron perforation.