Robert Honkanen

Long-term results of eyes with penetrating keratoplasty and glaucoma drainage tube implant.

PURPOSE To present long-term results of eyes with penetrating keratoplasty (PK) and glaucoma tube implant. DESIGN Retrospective, noncomparative, interventional case series. PARTICIPANTS We retrospectively reviewed medical records of all patients who underwent both PK and glaucoma tube implant (Baerveldt or Ahmed) at the University of Iowa between July of 1988 and December of 1997 (55 eyes). METHODS Success of the tube implant or PK was evaluated using Kaplan-Meier survival analysis. Association of relevant clinical factors with glaucoma or corneal graft outcome was evaluated using log-rank test or Cox proportional hazard regression analysis. The factors evaluated were glaucoma and cornea diagnoses; prior, simultaneous, and subsequent surgeries; type of tube implant; relative timing of surgeries; and postsurgical complications. MAIN OUTCOME MEASURES Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Corneal outcome was assessed by graft rejection, failure, and Snellen visual acuity. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS The mean preoperative intraocular pressure was 29.8 mmHg with an average of 2.9 medications. At last postoperative follow-up, the mean IOP decreased to 14.3 mmHg with 0.7 medication. The tube implant successfully controlled glaucoma in 45 eyes (82%) at 3 years. More severe postsurgical complications were associated with greater glaucoma failure. Graft rejection occurred in 17 eyes, and 7 of these progressed to failure. Nonimmunologic graft failure occurred in an additional 17 eyes (31%). The remaining 31 eyes (56%) had a clear graft. The corneal grafts remained clear in 70% and 55% of eyes at 2 and 3 years, respectively. Corneal graft failure was associated with glaucoma and cornea diagnoses groups, type of tube implant, and relative timing of the two surgeries. Complications occurred in 23 eyes (42%), and 10 of these were serious. CONCLUSIONS A drainage tube implant can successfully control glaucoma in a majority (82%) of keratoplasty eyes at 3 years. However, the success of corneal grafts is low (55%) at 3 years. Postsurgical complications are not uncommon and are associated with poor glaucoma outcome. Other clinical factors are associated with poor graft outcome.

Review and meta-analysis of ab-interno trabeculectomy outcomes

We analysed all of the PubMed publications on ab-interno trabeculectomy (AIT) with the Trabectome (Neomedix, Irvine, California, USA) to determine the reduction in intraocular pressure (IOP) and medications following the procedure. For IOP outcomes, PubMed was searched for ‘trabectome’, ‘ab interno trabeculotomy’ and ‘ab interno trabeculectomy’ and all available papers retrieved. The meta-analysis used a random-effects model to achieve conservative estimates and assess statistical heterogeneity. To investigate complications, we included all abstracts from the American Glaucoma Society, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery and the Association for Research in Vision and Ophthalmology. The overall arithmetic mean baseline IOP for standalone Trabectome was 26.71±1.34 mm Hg and decreased by 10.5±1.9 mm Hg (39% decrease) on 0.99±0.54 fewer medications. Defining success as IOP ≤21 with a 20% decrease while avoiding reoperation, the overall average success rate after 2 years was 46±34%. For combined phacoemulsification-Trabectome, the baseline IOP of 21±1.31 mm Hg decreased by 6.24±1.98 mm Hg (27% decrease) on 0.76±0.35 fewer medications. The success rate using the same definition at 2 years was 85±7%. The weighted mean IOP difference from baseline to study endpoint was 9.77 mm Hg (95% CI 8.90 to 10.64) standalone and 6.04 mm Hg (95% CI 4.95 to 7.13) for combined cases. Despite heterogeneity, meta-analysis showed significant and consistent decrease in IOP and medications from baseline to end point in AIT and phaco-AIT. The rate of visually threatening complications was <1%. On average, trabectome lowers the IOP by approximately 31% to a final IOP near 15 mm Hg while decreasing the number of medications by less than one, with a low rate of serious complications. After 2 years, the overall average success rate is 66%.

Correlation of automated visual field parameters and peripapillary nerve fiber layer thickness as measured by scanning laser polarimetry.

Purpose: To correlate Humphrey visual field mean sensitivity and peripapillary nerve fiber layer thickness as measured by scanning laser polarimetry. Methods: The authors studied 54 eyes of 34 patients who visited a university‐based glaucoma clinic and had undergone scanning laser polarimetry and Humphrey perimetry within 6 months. The study population included normal patients and those with glaucoma, ocular hypertension, and glaucoma suspect. The authors correlated visual field sensitivity with peripapillary nerve fiber thickness, and visual field mean deviation with the average deviation from the normal nerve fiber layer thickness. They also correlated the visual field mean deviation with all available GDx Nerve Fiber Analyzer parameters. Results: The visual field mean sensitivity and deviation showed a bilinear correlation to peripapillary nerve fiber layer thickness. The visual field mean sensitivity changed little when the nerve fiber layer thickness was greater than 70 μm. The nerve fiber layer thickness below this level was associated with a rapid decrease in the visual field sensitivity. Similarly, the visual field mean deviation was close to 0 dB when the nerve fiber layer was within ‐10 μm of the normal value; below this thickness, the mean deviation became substantially more negative. There was a large individual variability around the bilinear fit. Of the scanning laser polarimetry parameters, a calculated index, referred to as the number, had the highest correlation with the Humphrey mean deviation. Conclusion: The bilinear correlation and its variability between the scanning laser polarimetry and visual field parameters make it difficult to predict the result of one from the other. In general, the correlation between the two is better when there is a significant visual field defect than when the visual field is close to normal.

Effects of lowering cerebrospinal fluid pressure on the shape of the peripapillary retina in intracranial hypertension.

PURPOSE To analyze the deformations of the peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer in response to procedures that lower intracranial pressure (ICP). Second, to demonstrate how shape changes may complement the mean retinal nerve fiber layer (RNFL) thickness as a measure of intracranial hypertension (ICH) and papilledema. METHODS We used geometric morphometrics on spectral-domain optical coherence tomography images to analyze shape change of the ppRPE/BM layer after several interventions that lower cerebrospinal fluid (CSF) pressure. We also evaluated the effects of pressure-lowering interventions on both the anterior-posterior displacement of ppRPE/BM and the mean RNFL thickness. Forty-one patients with ICH and papilledema were studied before and after lumbar puncture (20), CSF shunt (9), and medical treatment of idiopathic ICH (23). We also compared the shape of 30 normal subjects to 23 patients whose papilledema resolved after medical treatment. RESULTS The ppRPE/BM-layer in ICH and papilledema is characterized by an asymmetric anterior deformation that moves posteriorly and becomes more V-shaped after each pressure-lowering intervention. The differences were statistically significant for all three groups. These shape changes also occur in patients with ongoing ICH who have secondary optic atrophy (without papilledema). Posterior displacement at the margin of the ppRPE/BM layer correlated strongly with overall shape changes. CONCLUSIONS The subsurface contour of the ppRPE/BM layer is a dynamic property that changes with CSF pressure-lowering interventions. It can supplement the RNFL thickness as an indirect gauge of ICP and is particularly helpful in patients with secondary optic atrophy. Direct measurements of displacement at the basement membrane opening may serve as a more convenient office-based surrogate for shape analysis.

Asymptomatic peripapillary subretinal hemorrhage: a study of 10 cases.

Background: Peripapillary subretinal hemorrhage (PSH) is often found together with optic disc drusen, optic disc edema, peripapillary subretinal neovascular membranes, vitreous traction, and bleeding diatheses. Previous reports have stated that such optic disc hemorrhages are associated with intrapapillary bleeding largely in patients of Asian origin who are visually symptomatic from this process. We have encountered patients with PSH who have clinical features that differ from those described in these reports. Methods: This is a retrospective observational case series. Medical records of 10 patients with isolated peripapillary subretinal hemorrhages were reviewed for clinical characteristics and ancillary testing, including demographics, history, complete eye examination, visual fields, fundus photos, ultrasound, and fluorescein angiography (four patients) at presentation and follow-up. We excluded patients with drusen, neovascular membranes, disc edema, and intrapapillary hemorrhages. Results: There were 10 patients, all white women without visual symptoms, who had isolated, monocular, nasal, or superonasal peripapillary subretinal hemorrhage, a dysplastic crowded-tilted optic disc, myopia, and normal visual function. The hemorrhages resolved without sequelae over 3-6 months. The findings were frequently discovered on routine examination and suspected of representing papilledema. Conclusions: We have described a benign syndrome of isolated PSH in crowded and tilted optic discs in myopic eyes of white women. The PSHs do not cause visual symptoms and resolve spontaneously. We propose that an interplay of ocular motor forces, scleral thinning, and vitreopapillary traction acting on a morphologically vulnerable optic disc explains these hemorrhages.

Optical coherence tomography shape analysis of the peripapillary retinal pigment epithelium layer in presumed optic nerve sheath meningiomas.

Background: Geometric morphometrics (GM) was used to compare the shape of the peripapillary retinal pigment epithelium–Bruchs membrane (ppRPE) layer imaged on spectral domain optical coherence tomography (SD-OCT) of patients with presumed optic nerve sheath meningiomas (pONSM) and normal subjects. Methods: We compared 2 groups: 30 normals to 10 patients (11 eyes) with pONSM. We digitized 20 equidistant semi-landmarks on OCT images of the ppRPE-layer, spanning 2500 &mgr;m on each side of the neural canal opening (NCO). Data were analyzed using standard GM techniques including a generalized least squares Procrustes superimposition, principal component analysis (PCA), thin-plate spline, and permutation statistical analysis to evaluate differences in shape. We also analyzed other variables with respect to shape including tumor size-proximity to the globe, age, retinal nerve fiber layer, and optic disc height. Results: All pONSM patients were female (age 37–66 years); 10 had unilateral and 1 had bilateral optic nerve involvement. Ten of the eyes had optic disc edema at presentation, 4 went on to develop shunt vessels, and 4 had optic atrophy. The ppRPE-layer bordering the NCO in normals is V-shaped pointing away from the vitreous; the ppRPE-layer in pONSM is indented causing an inverted-U shaped deformation skewed nasally toward the vitreous. PCA showed a significant difference between normals and pONSM (permutation, n = 10,000, P = 0.001). The size and proximity of the tumor to the globe correlates with the shape of the ppRPE-layer (r = 0.75, P = 0.04). Correlation between shape variables and RNFL thickening (r = 0.51), optic disc height (r = 0.67), and age (r = 0.67) were not statistically significant. Conclusion: The shape of the RPE layer in pONSM is characterized by an inverted-U shape or indentation that differs significantly from normals. It is indistinguishable from the shape we previously reported in papilledema and is not caused by disc edema. The mechanism in pONSM is unknown but may involve a change in the compliance of the nerve and/or localized sequestration of cerebrospinal fluid in the distal optic nerve sheath.

The use of endoscopic cyclophotocoagulation for moderate to advanced glaucoma

Endoscopic Cyclophotocoagulation (ECP) is a glaucoma surgery designed to reduce the intraocular pressure (IOP) by partially ablating the ciliary processes to decrease aqueous humour production and secretion. The aim of this paper is to review the literature regarding the background, indications and results of the surgery. Although there are case reports of visually devastating complications, including persistent hypotony and phthisis, the use of ECP is often reported in eyes with advanced diseases. When compared with both trabeculectomy and aqueous shunt implantation, the visual outcomes were better with ECP while the IOP outcomes were very similar. The evidence supports ECP as a very effective surgical option in recalcitrant glaucoma while some evidence supports its safety for use as a primary procedure.

Heterozygous triplication of upstream regulatory sequences leads to dysregulation of matrix metalloproteinase 19 in patients with cavitary optic disc anomaly

Patients with a congenital optic nerve disease, cavitary optic disc anomaly (CODA), are born with profound excavation of the optic nerve resembling glaucoma. We previously mapped the gene that causes autosomal‐dominant CODA in a large pedigree to a chromosome 12q locus. Using comparative genomic hybridization and quantitative PCR analysis of this pedigree, we report identifying a 6‐Kbp heterozygous triplication upstream of the matrix metalloproteinase 19 (MMP19) gene, present in all 17 affected family members and no normal members. Moreover, the triplication was not detected in 78 control subjects or in the Database of Genomic Variants. We further detected the same 6‐Kbp triplication in one of 24 unrelated CODA patients and in none of 172 glaucoma patients. Analysis with a Luciferase assay showed that the 6‐Kbp sequence has transcription enhancer activity. A 773‐bp fragment of the 6‐Kbp DNA segment increased downstream gene expression eightfold, suggesting that triplication of this sequence may lead to dysregulation of the downstream gene, MMP19, in CODA patients. Lastly, immunohistochemical analysis of human donor eyes revealed strong expression of MMP19 in optic nerve head. These data strongly suggest that triplication of an enhancer may lead to overexpression of MMP19 in the optic nerve that causes CODA.

Improved refractive outcomes of postgraduate year 4 cataract surgery after implementing a stepwise biometry lecture series reinforced by self-assessment at a teaching program

Purpose To determine whether a structured biometry course improves refractive outcomes of resident phacoemulsification. Setting Northeast Veterans Administration Hospital, Northport, New York, USA. Design Retrospective case study. Methods Phacoemulsification surgeries performed by residents before and after a biometry curriculum were reviewed. The inclusion criterion was phacoemulsification performed by residents. Patients with fewer than 3 months of follow‐up were excluded. The main outcome measure—the mean absolute difference between the target and final refraction—was compared using a linear mixed model. Results Phacoemulsification surgeries performed by 4 residents before (n = 223) and by 4 residents after (n = 242) a biometry curriculum was implemented were reviewed. All measured preoperative factors were similar in both groups, including age, visual acuity, axial length, steep and flat keratometry values, astigmatism, anterior chamber depth, and lens thickness. Before the biometry course was instituted, 10% of patients had a mean absolute difference of less than 0.25 diopter (D); the percentage was 35% afterward. The mean absolute difference was less than 0.50 D in 40% before the curriculum was initiated and 70% after. The mean absolute difference was less than 1.00 D in 75% before the curriculum was initiated versus 94% after (all P < .05). The corrected distance visual acuities were similar in both groups, with 83% and 80%, respectively, having an acuity of at least 20/25 (P > .05). Conclusion Residents’ refractive predictions significantly improved after a formal biometry curriculum, showing that improvements in resident surgical outcomes are possible with structured curriculums reinforcing outcome measures. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

iStent surgery as an option for mild to moderate glaucoma

Surgery with the iStent (Glaukos Corporation, Laguna Hills, CA, USA), a trabecular bypass stent, has been added as an option for the treatment of mild to moderate glaucoma. It is a 1 mm titanium stent used to directly shunt aqueous from the anterior chamber into Schlemm’s canal. The published literature indicates that it can be used in open-angle glaucomas to achieve an IOP in the mid-teens. No vision threatening complications related to the device have been reported.