Altered gene expression in conjunctival squamous cell carcinoma.

Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

Immunohistochemical expression and distribution of proteoglycans and collagens in sclerocornea.

To immunolocalize corneal keratan sulfate (KS) and its core protein lumican, aggrecan, type I and type III collagens in sclerocornea specimens and compare their expression and distribution to age-matched healthy corneas and scleras. Sclerocornea specimens (n = 3) and age-matched normal corneoscleral rim specimens (n = 3) were studied by light microscopy and histochemically. KS, lumican, aggrecan, type I and type III collagens were immunolocalized in the specimens using indirect immunofluorescence. The fluorescence intensity in each specimen was scored from 0 to 4, with 0 representing no fluorescence and 4 representing intense fluorescence. The sclerocornea specimens showed histologic features typical of sclerocornea. KS and lumican immunolabeling in the corneal stroma in sclerocornea was decreased, whereas aggrecan immunolabeling was increased compared to that seen in normal cornea and normal sclera. KS and lumican staining was more intense in the posterior part of sclerocornea specimens, whereas aggrecan staining was distributed throughout the stroma. The staining intensity and distribution of type I collagen in sclerocornea was similar to that seen in normal cornea. Type III collagen was faint to absent in both normal cornea and sclerocornea but strong labeling was noted in normal sclera. The immunophenotype of sclerocornea is similar to that of normal cornea but with reduced labeling intensity of KS and lumican and increased labeling intensity of aggrecan. This change could potentially contribute to the abnormal fibril assembly in sclerocornea.

Comparison of the efficacy of lotrafilcon B and comfilcon A silicone hydrogel bandage contact lenses after transepithelial photorefractive keratectomy.

Background: At completion of transepithelial photorefractive keratectomy (t-PRK) surgery, the eye is usually fitted with a bandage contact lens to reduce discomfort and promote epithelial healing. This study aimed to compare the outcomes of eyes fitted with lotrafilcon B versus comfilcon A, silicone hydrogel bandage contact lenses after t-PRK for the correction of low to moderate myopia, with or without astigmatism. Methods: In this comparative, prospective study, patients with myopia < -6 D with or without astigmatism (< 1.75 D), who underwent t-PRK between January and June 2018, were randomly allocated to the lotrafilcon B and comfilcon A groups. Preoperative characteristics, including age, sex, eye treated, uncorrected visual acuity (UCVA), best-corrected visual acuity, mesopic pupil size, central corneal thickness, and refractive error were recorded. Postoperatively, pain score, UCVA, and corneal epithelial defect size on days 1, 4, and 7 were compared between the two groups. Results: Twenty-nine eyes were included in each group. Demographic characteristics and preoperative measurements were similar between the two groups. UCVA was significantly improved on day 7 as compared to day 1 in the comfilcon A group (P = 0.03), but remained the same in the lotrafilcon B group (P = 0.70) as on day 1 postoperatively. There was no significant difference in UCVA between the two groups at any follow-up visits (all P > 0.05). The pain score on the first postoperative day was significantly higher in the lotrafilcon B-fitted eyes than in the comfilcon A group (P < 0.001), but was significantly reduced in both groups compared to day 1 (both P < 0.001). The epithelial defect in the comfilcon A group was significantly greater than in the lotrafilcon B group (P < 0.001) at day 1 postoperatively, with significant improvement in both groups (both P < 0.001). Conclusions: Healing responses were better with lotrafilcon B than with comfilcon A bandage contact lenses. The patients had a greater mean pain score with lotrafilcon B than with comfilcon A lenses on the first postoperative day, yet the final outcome was comparable between the two groups. We did not encounter any postoperative complications related to contact lens wear.

Changing trends in the clinical course and outcome of bacterial keratitis at King Khaled Eye Specialist Hospital.

OBJECTIVE: To evaluate changes in the predisposing factors and causative organisms, clinical course, and outcome of bacterial keratitis at King Khaled Eye Specialist Hospital (KKESH) between 1995 and 2005. METHODS: Retrospective review of 78 and 103 cases of culture-positive bacterial keratitis admitted to KKESH in 1995 and 2005. Main outcome measures Microbiological cure, visual outcome. RESULTS: There was little change in the predisposing factors for bacterial keratitis, initial clinical severity, or the microbiological profile between 1995 and 2005. While similar topical fortified antibiotic therapy regimens were used in both 1995 and 2005, there was a significant increase in the use of topical corticosteroids in 2005 (P < 0.001), either alone or in combination with medroxyprogesterone 1% and doxycycline. There were significant improvements in the percentage of eyes achieving microbiological cure with medical therapy alone (76.0 vs. 92.2%, P = 0.002) or in combination with surgical intervention (92.4 vs. 100.0%; P = 0.005). The percentage of eyes requiring enucleation or evisceration due to treatment failure declined significantly from 7.6 to 0% (P = 0.006). There was a significant improvement in the percentage of eyes achieving a final visual acuity > or =20/40 (10.1 vs. 29.1%, P = 0.001). CONCLUSIONS: Significantly better clinical outcomes were achieved in 2005 compared to 1995. Increased emphasis on management of inflammation in conjunction with the infectious process may have contributed to the improved outcomes.

Self-inflicted eye injury.

Individuals with a factitious ocular disorder feign or exaggerate having an eye injury or intentionally produce an eye injury so as to assume the role of a sick person. We report two cases of self-inflicted ocular injury using needle-like foreign bodies and razor that represent possible diagnoses of Munchausen syndrome. Both patients presented with different clinical pictures that misguided the clinical diagnosis and delayed proper management. Although self-inflicted ocular injuries are rare, ophthalmologists should be aware of the possibility of their existence, particularly when caring for patients with psychiatric conditions. SIMILAR CASES PUBLISHED: 13.

Late-onset donor-to-host transmission of Candida glabrata following corneal transplantation.

OBJECTIVE: To demonstrate the potential value of obtaining routine fungal cultures of donor rims at the time of corneal transplantation and instituting prophylactic therapy in culture-positive cases, even in the absence of clinical evidence of established microbial keratitis or endophthalmitis. METHODS: Interventional case report and literature review. RESULTS: A 69-year-old Saudi man underwent penetrating keratoplasty with donor tissue that was culture-positive for Candida glabrata. The postoperative course was complicated by slight override of the graft associated with an associated epithelial defect, but there was no evidence of microbial keratitis or significant anterior chamber inflammation. Following repair of the graft override on postoperative day 42, the epithelial defect healed. The subsequent clinical course was unremarkable until postoperative day 146, when a deep stromal infiltrate was present at the graft-host junction, associated with a dense endothelial plaque. Cultures of the anterior chamber were positive for Candida glabrata. Treatment with topical and intracameral amphotericin B and systemic fluconazole, along with topical corticosteroids and intracameral t-PA, was successful in eradicating the corneal infiltrate and resolving intraocular inflammation. Four months after treatment was initiated, there was no evidence of recurrent fungal keratitis or endophthalmitis. CONCLUSION: This case provides support for the practice of obtaining routine fungal cultures of donor rims at the time of corneal transplantation and for the implementation of prophylactic antifungal therapy in culture-positive cases.

Pathological and Immunohistochemical Alterations of the Cornea in Congenital Corneal Opacification Secondary to Primary Congenital Glaucoma and Peters Anomaly.

PURPOSE: To examine the immunohistochemical alterations in the corneal stroma in Peters anomaly (PA) and congenital glaucoma (CG) compared with age-matched normals and acquired adult corneal scarring (AACS). METHODS: The clinical features of PA and CG patients who underwent penetrating keratoplasty were recorded. Immunohistochemistry of cornea and control tissue (normal and acquired corneal scars) was performed with antibodies against collagen types I, III, keratan sulfate, lumican, decorin, and smooth muscle actin followed by semiquantitative analysis of immunolabeling. RESULTS: Clinical features in 2 groups were consistent with PA and CG. Microscopy showed thickened stromal collagen bundles in PA (n = 15), CG (n = 11), and AACS (n = 20) compared with normals (n = 18). PA and CG had distinct immunophenotypes compared with controls. Type I collagen labeling was more intense in CG compared with PA (intensity grading (IG) 2.73 vs. 2.07; P < 0.001). Decorin, lumican, and keratan sulfate labeling was significantly less intense in PA versus AACS (IG; 1.91, 0.38, 1.75 in PA and 2.7, 1.11, 2.61 in AACS. respectively; P = 0.002, P = 0.001 and P = 0.004) and normals (IG 1.92, 1.06, 2.59 respectively; P < 0.001, P < 0.001 and P = 0.005). Collagen I labeling was less intense in CG versus AACS (IG 2.73 vs. 3.09) (P = 0.007). Collagen III labeling was more intense in PA/CG than in normals (IG 0.9, 0.64, 0.62 retrospectively) (P < 0.001 in both). CONCLUSIONS: The immunophenotype of the corneal scar in PA and CG differs from normal corneas and so does PA from AACS. The similarities between CG and AACS suggest that CG scarring has an acquired component.

Association of aniridia and dry eyes.

PURPOSE: To study the association between congenital aniridia and dry eyes, and the status of limbal stem cells. DESIGN: Single-center, retrospective, noninterventional, comparative case series. PARTICIPANTS: Twenty patients (36 eyes) diagnosed with congenital aniridia. METHODS: Retrospective review of medical records at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia to identify all cases of congenital aniridia. Selected patients were requested to undergo further testing, especially for evaluation of dry eyes. Full ocular examinations were performed, including examination of the meibomian gland orifices and dry eye evaluation (by predetermined criteria of tear breakup time, tear meniscus level, presence of mucoid secretions, Schirmer's test with and without anesthesia, and fluorescein and rose Bengal staining patterns of the cornea and conjunctiva). Cytological evaluation was performed in 23 aniridic eyes by impression cytology to determine limbal stem cell status relative to control normal eyes. MAIN OUTCOME MEASURES: Abnormal tear film production and stability, meibomian gland dysfunction, severity of corneal involvement, and limbal stem cell deficiency. RESULTS: Twenty patients (36 eyes) diagnosed with congenital aniridia were classified into 3 groups according to the severity of corneal involvement: mild (2 eyes), moderate (21 eyes), and advanced (13 eyes) corneal changes. Tear breakup time was reduced by an average of 5 seconds in 90.7% of cases, tear meniscus levels were reduced to <0.5 mm in 88.6% of cases, and stenosed meibomian orifices were found in 77.8% of patients. Dry eyes (94%) correlated with the severity of corneal involvement (P = 0.001). Impression cytology revealed metaplasia in all tested cases. Furthermore, 8 of 23 eyes (35%) and 15 of 23 eyes (65%) had early and advanced limbal stem cell deficiency, respectively. CONCLUSIONS: Abnormal tear film stability and meibomian gland dysfunction are newly identified factors in patients with aniridia. Both correlate to the severity of ocular surface disease. Impression cytology is informative in diagnosing various degrees of limbal stem cell deficiency, which is present in all tested aniridia eyes.

Fixed dilated pupil after penetrating keratoplasty for macular corneal dystrophy and keratoconus.

PURPOSE: To identify predisposed eyes, risk factors, and protective measures and to evaluate methods of treatment for fixed dilated pupil after penetrating keratoplasty (PKP) for macular corneal dystrophy (MCD) and keratoconus. DESIGN: Retrospective observational case series. METHODS: A retrospective review was conducted of the charts of 195 patients who had PKP for MCD and of 1800 patients who had PKP for keratoconus at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. The review included an evaluation of the preoperative and intraoperative data and the postoperative course. In addition, clinical examinations at the last visit and photographs of the cornea, pupil, iris, and lens were analyzed. RESULTS: Twenty-one eyes of 18 patients had fixed dilated pupil after PKP; 15 eyes of 12 patients had MCD, and six eyes of six patients had keratoconus. A rise in intraocular pressure (IOP) during the procedure was seen in five patients (23.8%). Fixed dilated pupil was documented on the first and second postoperative days and the second postoperative week in 17 (80.9%), one (4.8%), and three (14.3%) eyes, respectively. Six eyes (28.6%) of six patients had severe eye inflammation. Only one eye (4.8%) regained partial reactivity of the pupil on follow-up visits. Seven eyes (33.3%) experienced lens changes; nine eyes (42.8%) had elevated IOP on the first postoperative day, and none of the eyes had chronic glaucoma. CONCLUSION: Inflammatory and multifactorial pathologic condition can cause fixed pupil after PKP. Atropine use, keratoconus, and high IOP are not constant findings in this syndrome. Awareness of the risk factors of fixed dilated pupil will help prevent against its occurrence.

Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models.

Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation.

Efficacy of punctal occlusion in management of dry eyes after laser in situ keratomileusis for myopia.

PURPOSE: To evaluate the effect of punctal plug use in preventing dry eye after laser in situ keratomileusis (LASIK). MATERIALS AND METHODS: A randomized clinical trial at a tertiary eye care center, Riyadh, Saudi Arabia. Participants underwent LASIK for myopia in both eyes and a lower punctal occlusion in one eye only while the other eye served as control. Both eyes received the same postoperative medications except for lubricant duration (subject eye: four times per day for one week; control eye: four times per day for 6 months). Participants were evaluated at 1 week, 2, and 6 months after surgery for signs and symptoms of dry eye. The main outcome measures were visual acuity; ocular surface parameters; and Ocular Surface Disease Index questionnaire. RESULTS: Seventy-eight eyes of 39 patients were included in this study. The Ocular Surface Disease Index scores of eyes with punctal plugs were better at all follow-up visits, and the differences between both eyes were statistically significant (1 week, p < 0.0001; 2 months, p < 0.0001; 6 months, p = 0.008). At the final follow-up visit, the percentage of normal eyes was higher in eyes with punctal plugs for all ocular surface parameters (Schirmer 1 test, 94.9%; tear breakup time, 77.8%; punctate epithelial keratitis score, 71.8%) compared to eyes without occlusion (Schirmer 1 test, 92.3%; tear breakup time, 58.3%; punctate epithelial keratitis score, 53.8%); however, such differences were not statistically significant. CONCLUSION: Punctal plug insertion after LASIK surgeries may minimize the need for frequent lubricant application and hence improve patient satisfaction.

Identification of multiple DNA copy number alterations including frequent 8p11.22 amplification in conjunctival squamous cell carcinoma.

PURPOSE: Little is known about the molecular alterations that drive formation and growth of conjunctival squamous cell carcinoma (cSCC). We therefore sought to identify genetic changes that could be used as diagnostic markers or therapeutic targets. METHODS: The DNA extracted from 10 snap-frozen cSCC tumor specimens and 2 in situ carcinomas was analyzed using array-based comparative genomic hybridization (aCGH), and further examined with NanoString and quantitative PCR. RESULTS: The number of regions of DNA loss ranged from 1 to 23 per tumor, whereas gains and amplifications ranged from 1 to 15 per tumor. Most large regions of chromosomal gain and loss were confirmed by NanoString karyotype analysis. The commonest alteration was amplification of 8p11.22 in 9 tumors (75%), and quantitative PCR analysis revealed 100-fold or greater overexpression of ADAM3A mRNA from 8p11.22 locus. In addition, recurring losses were observed at 14q13.2 and 22q11.23, both lost in 5 (42%) of the 12 tumors, and at 12p13.31, lost in 4 (33%) of the 12 samples. Of the eight loci associated with the DNA damage repair syndrome xeroderma pigmentosum, three showed loss of at least one allele in our aCGH analysis, including XPA (9q22.33, one tumor), XPE/DDB2 (11p11.2, one tumor) and XPG/ERCC5 (13q33.1, three tumors). CONCLUSIONS: Conjunctival SCC contains a range of chromosomal alterations potentially important in tumor formation and growth. Amplification of 8p11.22 and overexpression of ADAM3A suggests a potential role for this protease. Our findings also suggest that defects in DNA repair loci are important in sporadic cSCC.

Descemet's Stripping-Automated Endothelial Keratoplasty for Traumatic Aniridia and Aphakia.

This Interventional case reports a challenging case of descemet's stripping-automated endothelial keratoplasty (DSAEK) in a young male patient with traumatic aniridia, aphakia, and corneal edema. Surgery was planned in two stages; first was implantation of aniridia intraocular lens (AIOL), few months later, DSAEK procedure was performed. Successful outcome of both procedures was achieved as measured by the stability of the AIOL, clarity of the cornea, attachment of the lenticule, and improvement in vision. Aniridia implant supports a sufficient amount of air in the anterior chamber especially if the posterior segment is well formed, while providing the required lens power to improve vision. DSAEK procedure challenges that include iris defects and aphakia may be overcome by stepwise planning of the procedure.

Comparison of levobupivacaine 0.5% or bupivacaine 0.5% both in a mixture with lidocaine 2% for superficial extraconal blockade.

PURPOSE: To evaluate the quality and efficacy of Peribulbar blockade for superficial extraconal anesthesia with levobupivacaine 0.5% versus bupivacaine 0.5%, both combined with lidocaine 2% for patients undergoing phacoemulsification. MATERIALS AND METHODS: In this prospective, double blind study, 150 patients were randomly divided into two groups: group-1 received a Peribulbar block (PB) with a mixture of evobupivacaine 0.5% and lidocaine 2% while group-2 received a PB with a mixture of bupivacaine 0.5% and lidocaine 2%. The block was performed by insertion of a short needle (15 mm) in infra-temporal space just above inferior orbital notch. An initial volume of 6 9 ml of either mixture was injected until total upper eyelid drop. Akinesia score was assessed at 2, 5, and 10 min after the block. The degree of pain was assessed by a verbal rating scale immediately after block, at the end of surgery and 4 h postoperatively. The patients and surgeons were asked to rate their satisfaction level of the quality of block postoperatively. Data were analyzed with the unpaired, two-tailed t-test and the Chi-square test as appropriate. P < 0.05 was considered statistically significant. RESULTS: There were no significant differences between groups with respect to the akinesia score (P = 0.2) at 2, 5, and 10 min, the number of supplementary injections (P = 0.84) and initial and total required volume of local anesthetics (P = 0.80 and 0.81, respectively). There was no significant difference between the groups regarding surgeon and patient satisfaction (P = 0.53 and P = 0.74, respectively). Similarly the verbal rating scales assessed at three different occasions were not significantly different between the groups (P > 0.05 all cases). The need for additional intra-operative topical anesthetic was also similar between the groups. (P = 0.69). CONCLUSIONS: Superficial extra-conal block with a mixture of levobupivicaine 0.5% and lidocaine 2% or bupivicaine 0.5% and lidocaine 2% provides similar block quality and efficacy.

Spontaneous attachment of detached donor-corneal graft following Descemet's stripping automated endothelial keratoplasty.

This case report presents a case that had Descemet's stripping automated endothelial keratoplasty complicated postoperatively by detached donor grafts. The patient had a well centered partially detached graft that attached spontaneously the next day without the need to re-bubble. Postoperatively he had a clear cornea, improved uncorrected visual acuity with good endothelial cell count. It is worth waiting for a partially detached well centered graft to adhere spontaneously; this would lower the possible risks of repeated anterior chamber air injections. Cases should be selected to eliminate any mechanical factor that would prevent the attachment.

Ocular mycosis at a referral center in Saudi Arabia: A 20-year study.

PURPOSE: To review the clinical experience of fungal keratitis cases at King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia. METHODS: Retrospective observational review and analysis of 124 patient charts with confirmed diagnosis of fungal keratitis between 1984 and 2004. RESULTS: One hundred and twenty four eyes of 124 patients had proven fungal infection; 101 eyes had fungal keratitis and 23 eyes had fungal endophthalmitis complicating keratitis. Estimated proportion of fungal keratitis and endophthalmitis was 10.3%. Mean age was 55 years with male predominance (79.0%). Commonly associated factors were previous intraocular surgery (38.7%) and trauma (20.9%). Major risk factor for progressing to endophthalmitis was previous intraocular surgery (65.2%), p < 0.001. Initial laboratory results were fungal positive only in 30.6% (p < 0.001). Commonest organisms isolated were Aspergillus spp. (29.8%) followed by Trichophyton sp. (16.1%), then Candida and Fusarium sp. Comparison of both phases of the study showed improvement in the rate of successfully treated cases from 34.6% to 58.3%, and a decline in cases progressing to endophthalmitis from 25.0% to 13.9%. Therapeutic penetrating keratoplasty increased from 26.9% to 73.6% (p < 0.001). Thirteen eyes required enucleation or evisceration. CONCLUSIONS: In contrast to other studies on fungal keratitis, Aspergillusspp. and Trichophyton sp. were the most commonly isolated fungal pathogens; the former carries the worst prognosis. Risk factors included previous intraocular surgery and trauma. Poor outcome was associated with Aspergillus spp., delayed presentation, previous intraocular surgery and late surgical intervention. This study recommends early surgical intervention to improve the outcome.

Long-term corneal complication of retained anterior chamber-angle foreign body.

A 33-year-old patient referred to the cornea and anterior segment department to evaluate inferior corneal edema related to a retained intraocular foreign body (IOFB) in the anterior chamber-angle. The foreign body, which was a single piece of glass caused by an exploded light bulb twenty years back, was surgically removed; edema resolved and vision improved to 20/30. In the presence of an anterior chamber IOFB; long-term adverse effects should be considered. We would advise removal of the FB regardless of the inertness and location facts, as long as the risk and benefits of the surgical intervention are carefully evaluated.

Smallpox: An eradicated infection with persistent sequels - Case report and a brief on smallpox.

Sequelae of smallpox infection on the ocular surface are still seen, including corneal scars adherent leukoma and phthisical globes. This paper will report another sequel of smallpox infection causing inadvertent bleb in a 62-year-old diabetic female with no history of ocular surgery or trauma in either eye. The patient had smallpox infection during her childhood. Her follow up extended from May 1997 until August 2007 with a constant eye examinations including controlled intraocular pressure, avascular cystic inadvertent bleb, and up drown peaked pupil.