The effect of the glycemic control on the aqueous humor glucose levels in diabetic patients undergoing elective cataract surgery.

PURPOSE: Aqueous humor glucose levels play a role in the anterior segment disorders' pathophysiology, mainly in diabetics. Our purpose was to evaluate the ratio of aqueous humor glucose levels to blood glucose levels in diabetics and to evaluate the correlation between this ratio and blood glycated hemoglobin (HbA1c) levels. METHODS: This prospective study was performed in Sheba Medical Center during 2016-2018. The study included type 2 diabetic patients admitted for elective cataract surgery. Blood glucose levels were measured immediately before surgery. HbA1c was obtained within 3 months preoperatively. At the beginning of surgery, 0.05-0.1 mL aqueous humor was drawn. Main outcome measures were aqueous humor glucose/blood glucose ratio and the correlation between HbA1c and aqueous humor glucose/blood glucose ratio. RESULTS: Thirty-seven patients (mean age 75.2 ± 11.2 years) were recruited. The average aqueous humor glucose/blood glucose ratio was 0.69 ± 0.20. A significant positive correlation was found between aqueous humor and blood glucose levels, Pearson coefficient constant R = 0.63 (p < 0.01), and specifically stronger among older patients R = 0.89 (p < 0.01), females R = 0.74 (p < 0.01), patients with short-term disease (<10 years) R = 0.80 (p < 0.01), and patients treated with oral anti-diabetic treatment R = 0.74 (p < 0.01). A significant strong positive correlation was found between HbA1c levels and aqueous humor glucose/blood glucose ratio R = 0.62 (p < 0.01), and specifically stronger among older patients R = 0.82 (p < 0.01), males R = 0.70 (p < 0.01), patients with prolonged disease (⩾10 years) R = 0.540 (p < 0.05), and patients treated with oral anti-diabetic treatment R = 0.62 (p < 0.01). CONCLUSION: A significant strong correlation was found between aqueous humor glucose levels and blood glucose levels. Poor glycemic control was strongly correlated with an increased ratio, reflecting an increased anterior chamber's glucose permeability. Older age group was found to have stronger correlation of poor glycemic control with this ratio.

Safety of cataract surgery in patients treated with the new oral anticoagulants (NOACs).

PURPOSE: To evaluate the safety of phacoemulsification of cataract in patients taking new oral anticoagulants (NOACs). METHODS: In a prospective case series, consecutive patients on NOACs (dabigatran, rivaroxaban, or apixaban) who were referred for uncomplicated cataract surgery to the eye institute underwent a thorough ophthalmological and hematological evaluation. Rivaroxaban and apixaban anti-factor Xa tests, and diluted thrombin time for dabigatran, were used for monitoring anticoagulation levels in blood. Blood was drawn for these tests just prior to surgery and at a peak level of the drug at about 4 h post-surgery (2 h after the drug was given). All surgeries were videotaped and patients were examined at 1 and 7 days after the operation. The main outcome measures included assessment of intra-operative, postoperative ocular bleeding, and other related complications. RESULTS: Thirty-five eyes of 25 unrelated patients ranging in age from 63 to 92 years (mean 77.6 years) underwent phacoemulsification. Intra-operative bleeding was observed in 5 eyes from the conjunctiva or limbus at the main incision site. No intraocular bleeding occurred. No hemorrhagic complications were observed during the 1-week follow-up. According to anti-factor Xa levels prior to surgery and following surgery, 85% of the patients were on therapeutic levels of NOACs. CONCLUSIONS: Clear corneal incision phacoemulsification performed under topical anesthesia can be safely performed in simple cases of cataract without discontinuing NOAC treatment.

Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis.

BACKGROUND: Therapy of S. aureus keratitis is increasingly challenging due to emerging resistant strains. Staphylolysin (LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of the current study was to study the effect of treatment with staphylolysin on experimental keratitis caused by various Staphylococcus aureus strains. METHODS: The therapeutic effect was studied in a keratitis model induced in rabbits by intrastromal injections of 10(3) S. aureus cells of three different methicillin-resistant S. aureus (MRSA) strains and one methicillin-susceptible S. aureus strain (MSSA). Topical treatment with either staphylolysin or bovine serum albumin (BSA; control) was applied every half hour for 5 h, starting at 4 h after infection. Corneas were removed for bacterial quantification. Histopathological analysis was performed on MSSA-infected rabbits, killed at either one or 84 h after completion of treatment and on uninfected eyes 1 h after treatment termination. RESULTS: The number of bacteria in the staphylolysin-treated corneas was significantly reduced in all infections with the four S. aureus strains studied as compared to controls: the staphylolysin-treated eyes infected with MRSA strains were either completely sterilized or showed a 3-4 orders of magnitude decrease in the number of cfu/cornea (p = 0.004 to 0.005); all of the staphylolysin-treated MSSA-infected eyes were sterile. Histopathological analysis of the methicillin-sensitive (MSSA) strain-infected eyes at 84 h after completion of treatment showed moderate inflammation in the staphylolysin-treated eyes as compared with extensive abscess formation in the control group. The uninfected corneas showed only mild stromal edema in both the staphylolysin and BSA-treated groups. CONCLUSIONS: Staphylolysin provided long-lasting protection against several strains of S. aureus, evident by both its strong anti-bacterial activity and beneficial histopathological results of treatment.

Consecutive appearance of corneal subepithelial infiltrates after intravitreous bevacizumab injections.

PURPOSE: To report a case of corneal subepithelial infiltrates appearing after intravitreous bevacizumab injections. METHODS: A review of the patient's history and clinical examination findings in a patient who had epidemic keratoconjunctivitis more then 20 years before treatment with bevacizumab for age-related macular degeneration. RESULTS: After the third and fourth bevacizumab injections, the patient presented with unilateral corneal subepithelial infiltrates. The infiltrates were accompanied by mild anterior chamber reaction and resolved with topical steroid treatment. CONCLUSIONS: Treatment with intravitreous bevacizumab may precipitate an immune response leading to the appearance of corneal subepithelial infiltrates.

Differences in the corneal biomechanical effects of surface ablation compared with laser in situ keratomileusis using a microkeratome or femtosecond laser.

PURPOSE: To compare the effects of different flap creation techniques on the biomechanical properties of the cornea in patients having myopic laser refractive surgery. SETTING: UCLA Laser Refractive Center of the Jules Stein Eye Institute, Los Angeles, California, USA. METHODS: In this retrospective case series, eyes that had myopic laser refractive surgery were categorized according to the type of flap creation: mechanical microkeratome (MK) LASIK (n=32), femtosecond laser (FSL) LASIK (n=32), or no flap creation (PRK) (n=33). The preoperative central corneal thickness, intraoperative flap thickness, and planned ablation depth (AD),and the preoperative and postoperative manifest refraction spherical equivalent, corneal hysteresis (CH), and corneal resistance factor (CRF) were recorded. RESULTS: The mean change in CH (DeltaCH) was 2.2 mm Hg, 1.9 mm Hg, and 2.3 mm Hg in the MK, FSL, and PRK groups, respectively. There were no significant differences in AD, DeltaCH, or DeltaCRF between the 3 groups. The correlation between AD and DeltaCH was significant in all 3 groups. The correlation was strongest in the FSL group (r=0.82, P<.0001) and weaker in the PRK group (r=0.47, P= .006) and MK group (r=0.46, P= .008). CONCLUSIONS: The biomechanical measures of CH and CRF decreased similarly after PRK and LASIK using laser or mechanical flap creation. However, LASIK using femtosecond laser flap creation caused a significantly more predictable change in corneal biomechanics, which correlated strongly with AD, than the change with PRK and LASIK with microkeratome flap creation.

Corneal biomechanical measurements before and after laser in situ keratomileusis.

PURPOSE: To study the correlation between corneal biomechanical properties and surgical parameters in myopic patients before and after laser in situ keratomileusis (LASIK). SETTING: UCLA Laser Refractive Center of the Jules Stein Eye Institute, Los Angeles, California, USA. METHODS: In 43 eyes of 43 patients, the Ocular Response Analyzer was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated IOP (IOPcc) before and 1 month after LASIK. Manifest refraction spherical equivalent (MRSE), preoperative central corneal thickness (CCT), flap thickness (FT), and ablation depth (AD) were also recorded. Changes in these parameters after LASIK were calculated and the correlations between the change in CH (DeltaCH), change in CRF (DeltaCRF) and the AD, change in MRSE (DeltaMRSE), and CCT were examined. The relationship between DeltaCRF and DeltaMRSE was examined by linear regression analysis. RESULTS: The preoperative mean CH and mean CRF (11.52 mm Hg +/- 1.28 [SD] and 11.68 +/- 1.40 mm Hg, respectively) were significantly higher than postoperative values (9.48 +/- 1.24 mm Hg and 8.47 +/- 1.53 mm Hg, respectively) (P < .0001). A higher attempted correction was correlated with a larger DeltaCH and DeltaCRF (AD, r = 0.47 and r = 0.65, respectively; DeltaMRSE, r = 0.51 and r = 0.66, respectively). No correlation was found between DeltaCH, DeltaCRF, and preoperative CCT. CONCLUSIONS: Changes in CH and CRF after LASIK suggest alteration in corneal biomechanics correlating with attempted correction. The CRF parameter may be more useful than the CH parameter in assessing biomechanical changes resulting from LASIK.

A novel variant of combined granular-lattice corneal dystrophy associated with the Met619Lys mutation in the TGFBI gene.

OBJECTIVE: To report a novel mutation in TGFBI (GenBank NM_000358), p.Met619Lys, associated with a variant of combined granular-lattice corneal dystrophy. METHODS: Slitlamp examination and DNA collection from the proband and affected and unaffected relatives. All 17 exons of TGFBI were amplified and sequenced in the proband. Exon 14 was amplified and sequenced in the proband's family members and in 100 controls. Histopathologic examination of the excised corneal buttons from the proband and 3 family members was also performed. RESULTS: Affected individuals demonstrated an age-dependent phenotype, with the progression from central subepithelial needlelike deposits in younger individuals to polymorphic anterior stromal opacities in older family members. Screening of TGFBI in the proband demonstrated a novel mutation, p.Met619Lys, which was also present in all affected family members. Histopathologic examination revealed stromal deposits that stained with the Congo red and Masson trichrome stains as well as an antibody to the protein product of TGFBI. CONCLUSIONS: We present a unique corneal dystrophy phenotype associated with the novel p.Met619Lys mutation in TGFBI. Clinical Relevance The atypical and variable phenotype and the demonstration of both hyaline and amyloid stromal deposits indicate that neither clinical nor histopathologic features may be relied on to accurately diagnose and classify the corneal dystrophies.

Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy.

PURPOSE: To identify the genetic basis of Schnyder crystalline corneal dystrophy (SCCD) through screening positional candidate genes and UBIAD1, in which mutations have been associated with SCCD, in affected families. METHODS: The coding region of each of the 16 positional candidate genes for which mutation screening has not been previously reported was screened with polymerase chain reaction (PCR) amplification and automated sequencing in four affected individuals from two families with SCCD. In addition, the coding region of UBIAD1, located just outside of the originally described SCCD candidate interval on chromosome 1p36, was directly sequenced in affected and unaffected individuals from three families with SCCD. RESULTS: Eighteen novel and 15 previously reported sequence variants were identified in 10 of the 16 positional candidate genes. Only two of the sequence variants segregated with the affected phenotype in either of the families screened. Both were novel single nucleotide polymorphisms (SNPs) predicted to result in synonymous amino acid substitutions in different predicted genes. However, one of these SNPs was also identified in control individuals, and the other SNP was not predicted to alter splicing. Screening of UBIAD1 revealed a different missense mutation in each of the three unrelated probands that was screened: p.Asn102Ser, p.Arg119Gly, and p.Leu121Val. Screening of the affected and unaffected relatives of the probands in whom the p.Asn102Ser and p.Leu121Val mutations were identified demonstrated that each mutation segregated with the affected phenotype. None of the three missense mutations was identified in 110 control individuals. CONCLUSIONS: No presumed pathogenic coding region mutations were identified in the genes mapped to the candidate region for SCCD. However, missense mutations in UBIAD1, located just outside of the originally described SCCD fine mapped region, were identified in each of the three families with SCCD, confirming that mutations in UBIAD1 are associated with SCCD.

Posterior polymorphous corneal dystrophy is associated with TCF8 gene mutations and abdominal hernia.

Mutations in the two-handed zinc-finger homeodomain transcription factor gene (TCF8) have been associated with posterior polymorphous corneal dystrophy (PPCD) and extraocular developmental abnormalities. We performed screening of TCF8 in 32 affected, unrelated probands, affected and unaffected family members of probands identified with a TCF8 mutation, and in 100 control individuals. Eight different pathogenic mutations were identified in eight probands: four frameshift (c.953_954insA, c.1506dupA, c.1592delA, and c.3012_3013delAG); three nonsense (Gln12X, Gln214X, Arg325X); and one missense (Met1Arg). Screening of TCF8 in affected and unaffected family members in six families demonstrated that each identified mutation segregated with the disease phenotype in each family; two probands did not have additional family members available for analysis. None of the eight TCF8 mutations was identified in 200 control chromosomes. The prevalence of hernias of the abdominal region in affected individuals with PPCD associated with TCF8 mutations was significantly higher than the prevalence in both individuals with PPCD not associated with a TCF8 mutation and in unaffected individuals. Therefore, PPCD is associated with TCF8 mutations in one quarter of affected families in this study, or about one third of all PPCD families that have been screened thus far. In these families, the presence of apparently causative TCF8 mutations is associated with abdominal and inguinal hernias.

Autosomal recessive CHED associated with novel compound heterozygous mutations in SLC4A11.

PURPOSE: To determine the genetic basis of autosomal recessive congenital hereditary endothelial dystrophy (CHED2) in an American patient of Chinese ancestry. METHODS: Slit-lamp examination of the proband and his parents, as well as histopathologic examination of excised corneal specimens from the proband, were performed to confirm the diagnosis of autosomal recessive CHED. DNA was collected from the proband and his parents, and all 19 exons of the SLC4A11 gene were amplified and screened. RESULTS: The proband showed diffuse bilateral corneal edema, which was not present in either of his parents. After the performance of bilateral penetrating keratoplasties, histopathologic examination of the excised corneal specimens showed marked corneal stromal edema and an absence of corneal endothelial cells. Screening of SLC4A11 showed 2 heterozygous mutations: c.743G>A (Ser232Asn) and c.1033A>T (Arg329X). The proband's mother was found to be heterozygous for the Ser232Asn missense mutation, and his father was heterozygous for the Arg329X nonsense mutation. No other coding region sequence variants were identified in the proband or his parents, and neither of the identified mutations was identified in 100 control individuals. CONCLUSIONS: CHED2 is associated with mutations in SLC4A11, a member of the SLC4 family of base transporters. Although the majority of affected individuals reported to date have shown homozygous mutations, associated with consanguinity in the Burmese, Indian, and Pakistani populations, we report 2 novel, independently sorting SLC4A11 mutations in an affected individual of Chinese ancestry.

Keratoconus is not associated with mutations in COL8A1 and COL8A2.

PURPOSE: To evaluate the suggested role of the COL8A1 and COL8A2 genes in the pathogenesis of the corneal ectatic disorders keratoconus and keratoglobus through mutation screening in affected patients. METHODS: DNA extraction, polymerase chain reaction amplification, and sequencing of COL8A1 and COL8A2 were performed in 50 unrelated keratoconus and 2 unrelated keratoglobus patients. RESULTS: No sequence variations were identified in COL8A1 and COL8A2 in the 2 patients with keratoglobus. Screening of COL8A1 in keratoconus patients revealed a previously identified single nucleotide polymorphism (SNP; c.1850C>T; Pro535Pro), in 1 patient. Screening of COL8A2 in keratoconus patients revealed 7 previously described SNPs: c.14G>A (Gly3Arg); c.112G>A (Ala35Ala); c.1012C>G (Leu335Leu); c.1308G>A (Arg434His); c.1492G>A (Gly495Gly); c.1512C>T (Thr502Met); and c.1765C>T (Pro586Pro). Four novel sequence variants were also identified, each in 1 affected patient: c.38_40dupCTG (Leu11dup), also identified in an unaffected relative of the affected proband, c.667G>A (Gly220Gly), c.1588G>A (Pro527Pro), and c.2026C>T (Val673Val). None of the 3 novel synonymous substitutions identified in COL8A2 was predicted to produce a splice acceptor site. CONCLUSIONS: The absence of pathogenic mutations in COL8A1 and COL8A2 in patients with keratoconus indicates that other genetic factors are involved in the pathogenesis of this corneal ectatic disorder.

Risk for eye splash injury during administration of intraocular injections: a study of retina specialists and fellows.

OBJECTIVE: To evaluate the use of eye protection and frequency of eye splash events during intraocular injections as well as infection risk awareness among retina specialists and fellows in training. METHODS: In a prospective survey of practicing retina specialists and retina fellows, frequency of use and type of eye protection employed during intraocular injections, frequency of eye splash occurrences, description of the eye splash event, number of procedures performed, and awareness of transconjunctival infection risk were investigated. RESULTS: Sixty-four ophthalmologists responded to the questionnaire: 40 retina fellows and 24 retina specialists. The response rate was 100%. Twenty-five percent of the fellows and 33.3% of the specialists reported using eye protection, including corrective glasses, during all intraocular injections. Two of the retina fellows and none of the specialists used special forms of eye protection. Retina fellows had a mean +/- SD of 2.1 +/- 1.3 years experience and the specialists had a mean +/- SD of 10.4 +/- 6.7 years experience in performing intraocular injections. The mean number of injections +/- SD performed by the fellows and specialists was 23 +/- 14.6 and 35 +/- 11.9 per month, respectively. Twelve conjunctival or corneal splash occurrences were reported by six fellows and two retina specialists. Eleven splash events occurred due to reflux of fluid during administration of subconjunctival anesthetic injection, and one event occurred during an anterior chamber tap. Splash events were significantly more likely to occur during procedures performed by fellows, with a relative risk of 8.4 for unprotected procedures (P< 0.001, Fisher exact test). Most (87.5%) of the participants were aware of the risk for transconjunctival viral infection. CONCLUSION: Special eye protection is seldom used during administration of intraocular injections. Although the risk for eye splash during administration of subconjunctival anesthetic before intraocular injections is relatively small, protective measures may be considered when treating high-risk patients.

Autosomal dominant cornea plana is not associated with pathogenic mutations in DCN, DSPG3, FOXC1, KERA, LUM, or PITX2.

PURPOSE: To determine the genetic basis of autosomal dominant cornea plana (CNA1) through the performance of a genome-wide linkage analysis and screening of the decorin (DCN), dermatan sulfate proteoglycan 3 (DSPG3), forkhead box C1 (FOXC1), keratocan (KERA), lumican (LUM,) and paired-like homeodomain transcription factor 2 (PITX2) genes in members of an affected multigenerational family. METHODS: Cycloplegic refraction, slit lamp biomicroscopy, corneal pachymetry, and corneal topography were performed to determine each patient's affected status. DNA was obtained from affected and unaffected subjects for the performance of a genome-wide linkage analysis as well as PCR amplification and sequencing of DCN, DSPG3, FOXC1, KERA, LUM, and PITX2. RESULTS: Five affected and three unaffected individuals were examined and provided a peripheral blood sample for DNA isolation. All affected individuals demonstrated an average corneal dioptric power less than 39 D, as well as one or more of the following anomalies: high hyperopia, strabismus, microcornea, posterior embryotoxon, iridocorneal adhesions, iris atrophy, and pupillary irregularities. A genome-wide linkage analysis did not indicate or exclude linkage to the region on chromosome 12 to which CNA1 has been previously mapped, and did not provide a single or multipoint LOD score greater than 2.0 for any of the 400 microsatellite markers. Screening of DCN, DSPG3, FOXC1, KERA, LUM, and PITX2 revealed 12 previously described single nucleotide polymorphisms, 2 previously described duplications, and 1 previously described insertion. None of the mutations previously associated with autosomal recessive cornea plana (CNA2) were identified. Seven novel sequence variants were described, including 5 single nucleotide substitutions, 1 insertion and 1 deletion. None of the identified sequence variants demonstrated complete segregation with the affected phenotype in the pedigree. CONCLUSION: Although missense and nonsense mutations in KERA are associated with CNA2, we did not identify any of the previously described mutations or novel mutations that segregated with the disease phenotype in a family with CNA1. In addition, no pathogenic sequence variations were found in DCN, DSPG3, LUM, PITX2 and FOXC1, which have also been implicated in corneal and anterior segment dysgenesis.

The slower the better: on the instability of gas jets in a model of pneumatic retinopexy.

PURPOSE: To investigate the effect of injection technique parameters on the formation of multiple gas bubbles in a porcine eye model for pneumatic retinopexy. METHODS: Three hundred twenty-four adult porcine eyes were injected with 0.4 mL of C3F8 with variations in the depth of injection, speed of injection, and size of needle bore. The number of gas bubbles in the eye was assessed with indirect ophthalmoscopy. RESULTS: Shallow injections resulted in a higher incidence of a single bubble than did deep injections (P < 0.001; Fisher exact and Wilcoxon rank sum tests). Slow injections were significantly advantageous in producing a single gas bubble during shallow as well as during deep injections (P < 0.001, Fisher exact and Wilcoxon rank sum tests). With a shallow needle insertion, the slow speed of injection produced a single bubble in 75.9% of the eyes, whereas moderately brisk injections resulted in one bubble in 50.9% of the eyes. During deep needle insertion, 44.4% of the eyes had one bubble if the gas was injected slowly and only 11.1% had a single bubble with moderately brisk gas injections. The bore of the needle did not significantly change the number of bubbles during deep or shallow injections. CONCLUSIONS: The factors that were found to be important in reducing the formation of multiple gas bubbles in the eye were shallow depth of injection and slow speed of gas delivery.

Endocrine effects on the growth, development and function of the eye.

A cohort of hormonal signals affects the function of the eye in providing eyesight. From the early days of growth, endocrine mechanisms guide the young eye's development. Later on in life, hormonal interactions play an important role in maintaining proper vision and continue to affect the eyes in pregnancy, as well as in aging. The purpose of this article is to review the effects of the endocrine system on the eye. Current knowledge about hormonal interactions that play a role in the growth and development of the eye will be discussed separately for each of the hormones known to be involved.

[Ocular manifestations of rickettsial diseases].

Rickettsial infection may cause severe systemic disease. The ocular manifestations of rickettsial infection may include sub-conjunctival hemorrhages, corneal abscesses, uveitis, optic nerve head edema, retinal vasculitis hemorrhages and infiltrates and endophthalmitis. Ocular complications may result in significant visual loss. Ocular manifestations may precede other systemic signs and symptoms and assist in clinical diagnosis. This report describes two cases with ocular involvement of rickettsial disease.

Primary congenital upper eyelid retraction in infants and children.

Four infants with unilateral or bilateral eyelid retraction were examined. A full clinical evaluation revealed no ocular or systemic pathology. In all cases, clinical examination, thyroid function tests, and neuroimaging of the brain and orbits revealed no underlying disease process. The eyelid retraction did not change over the follow-up period of 2 to 6 years. Unilateral or bilateral eyelid retraction in infants and children may be an isolated clinical entity without an associated underlying disease.

Eyelid splitting and extirpation of hair follicles using a radiosurgical technique for treatment of trichiasis.

BACKGROUND AND OBJECTIVE: To describe a new, simple, and rapid surgical modification for the treatment of trichiasis. PATIENTS AND METHODS: In this noncomparative, prospective, interventional case series, 12 eyelids of 8 consecutive patients suffering from acquired trichiasis were treated by splitting the eyelid margin using a radiosurgical technique and then extirpating the hair follicles. The main outcome measure was successful resolution of trichiasis without recurrence during a follow-up period of at least 1 year. RESULTS: Complete recovery of the trichiatic eyelashes at the site of the treatment occurred in 10 of the 12 eyelids treated. There were no complications during or after healing of the surgical wound during the follow-up period. CONCLUSION: Radiosurgery provides a simple and rapid modification of the surgical treatment for acquired trichiasis, with good functional results.