M. la Cour

Value of internal limiting membrane peeling in surgery for idiopathic macular hole stage 2 and 3: a randomised clinical trial.

Aim: To determine the effect of internal limiting membrane (ILM) peeling on anatomical and functional success rates in stage 2 and 3 idiopathic macular hole surgery (MHS). Methods: Randomised clinical trial of stage 2 and 3 idiopathic macular hole without visible epiretinal fibrosis and with less than 1 year’s duration of symptoms. Eyes were randomised to (1) vitrectomy alone without retinal surface manipulation, (2) vitrectomy plus 0.05% isotonic Indocyanine Green (ICG)-assisted ILM peeling or (3) vitrectomy plus 0.15% Trypan Blue (TB)-assisted ILM peeling. Main outcomes were hole closure after 3 and 12 months and best-corrected visual acuity after 12 months. Results: 78 eyes were enrolled. Primary closure rates were significantly higher with ILM peeling than without peeling for both stage 2 holes (ICG peeling 100%, non-peeling 55%, p = 0.014) and for stage 3 holes (ICG peeling 91%, TB peeling 89%, non-peeling 36%, p<0.001). Visual outcomes in eyes with primary hole closure were not significantly different between the groups. Conclusions: Dye-assisted ILM peeling was associated with significantly higher closure rates than non-peeling in both stage 2 and 3 MHS. Intraoperative ILM staining with 0.05% isotonic ICG was not associated with a significantly different visual outcome than non-peeling or TB peeling in eyes with primary hole closure. Trial registration number: NCT00302328.

Cotransport of H+, lactate and H2O by membrane proteins in retinal pigment epithelium of bullfrog.

1. The interaction between H+, lactate and H2O fluxes in the retinal membrane of the pigment epithelium from bullfrog Rana catesbiana was studied by means of ion‐selective micro‐electrodes. 2. Changes in intracellular pH and cell volume were recorded in response to abrupt changes in retinal solution concentration and/or osmolarity. 3. Two parallel pathways for water transport were identified across the retinal membrane, an osmotic one with a hydraulic water permeability of 3.2 x 10(‐4) cm s‐1 (osmol l‐1)‐1 and one which depended on the presence of lactate. 4. Addition of sodium lactate to the retinal solution caused cell shrinkages that were small compared with those produced by mannitol. The reflection coefficient for sodium lactate was 0.25. 5. Isosmotic replacement of Cl‐ with lactate caused an influx of water. Simultaneous acidification of the retinal solution from pH 7.4 to 6.4 enhanced the effect. The influx of water could proceed against osmotic gradients elicited by mannitol. 6. The interdependence of the fluxes of H+, lactate and H2O can be described as cotransport: the fluxes had a fixed ratio of about 109 mmol of lactic acid per litre of water, the flux of one species was able to energize the flux of the other two, and the fluxes exhibited saturation for increasing driving forces. 7. The Gibbs equation gives an accurate quantitative description of these coupled fluxes.

Vitrectomy with Internal Limiting Membrane Peeling versus No Peeling for Idiopathic Full-Thickness Macular Hole

OBJECTIVE To determine whether internal limiting membrane (ILM) peeling improves anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery when compared with the no-peeling technique. DESIGN Systematic review and individual participant data (IPD) meta-analysis undertaken under the auspices of the Cochrane Eyes and Vision Group. Only randomized controlled trials (RCTs) were included. PARTICIPANTS AND CONTROLS Patients with idiopathic stage 2, 3, and 4 FTMH undergoing vitrectomy with or without ILM peeling. INTERVENTION Macular hole surgery, including vitrectomy and gas endotamponade with or without ILM peeling. MAIN OUTCOME MEASURES Primary outcome was best-corrected distance visual acuity (BCdVA) at 6 months postoperatively. Secondary outcomes were BCdVA at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12 months; primary (after a single surgery) and final (after >1 surgery) macular hole closure; need for additional surgical interventions; intraoperative and postoperative complications; patient-reported outcomes (PROs) (EuroQol-5D and Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness. RESULTS Four RCTs were identified and included in the review. All RCTs were included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs. No evidence of a difference in BCdVA at 6 months was detected (mean difference, -0.04; 95% confidence interval [CI], -0.12 to 0.03; P=0.27); however, there was evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean difference, -0.09; 95% CI, -0.17 to-0.02; P=0.02). There was evidence of an effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95% CI, 4.98-17.24; P<0.00001) and final macular hole closure (OR, 3.99; 95% CI, 1.63-9.75; P=0.02) and less requirement for additional surgery (OR, 0.11; 95% CI, 0.05-0.23; P<0.00001), with no evidence of a difference between groups with regard to intraoperative or postoperative complications or PROs. The ILM peeling was found to be highly cost-effective. CONCLUSIONS Available evidence supports ILM peeling as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.

Optic nerve oxygen tension: effects of intraocular pressure and dorzolamide

AIM To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide. METHODS Domestic pigs were used as experimental animals. Oxygen tension was measured by means of a polarographic electrode in the vitreous 0.5 mm anterior to the optic disc. This entity is called the optic nerve oxygen tension. Intraocular pressure was controlled by a hypodermic needle inserted into the anterior chamber and connected to a saline reservoir. RESULTS When the intraocular pressure was clamped at 20 cm H2O optic nerve oxygen tension was 20 (5) mm Hg (n=8). Intravenous administration of dorzolamide caused an increase in optic nerve oxygen tension of 43 (8)% (n=6). Both before and after administration of dorzolamide optic nerve oxygen tension was unaffected by changes in intraocular pressure, as long as this pressure remained below 60 cm H2O. At intraocular pressures of 60 cm H2O and below, dorzolamide significantly increased optic nerve oxygen tension. CONCLUSION Intravenous administration of 500 mg dorzolamide increases the oxygen tension at the optic nerve head during acute increases in intraocular pressure.

Potassium transport of the frog retinal pigment epithelium: autoregulation of potassium activity in the subretinal space.

The K+ transport of the isolated retinal pigment epithelium from the bull‐frog was studied using micropuncture with double‐barrelled ion‐selective micro‐electrodes. Transient changes of intracellular values of electrical potential and K+ activity were monitored in response to abrupt changes in the K+ concentration on the retinal side of the tissue. The data were interpreted in terms of a simple three‐compartment model of the epithelium in which the retinal (or apical) and choroidal (or basal) membranes separate the cellular compartment from the retinal and choroidal compartments. K+ transport across the retinal membrane was described by an active ouabain‐sensitive K+ influx in parallel with a passive electrodiffusive K+ efflux. In steady state under control conditions, the active K+ influx (pump rate) averaged 0.18 X 10(‐9) mol cm‐2 s‐1. The electrodiffusive K+ efflux was described by a K+ permeability, which in steady state under control conditions averaged 1.7 X 10(‐5) cm s‐1. K+ transport across the choroidal membrane was described as purely electrodiffusive. In steady state under control conditions, the K+ permeability of the choroidal membrane averaged 0.6 X 10(‐5) cm s‐1. When the K+ concentration on the retinal side of the tissue was increased from its control value, the K+ permeability of the retinal membrane decreased and the K+ permeability of the choroidal membrane increased. This caused the epithelium to attain a new steady state in which the cells transported K+ away from the retinal compartment at a high rate. When the K+ concentration on the retinal side of the tissue was decreased from its control value, the K+ permeability of the retinal membrane increased and the pump rate decreased. This caused the epithelial cells to transport K+ from the cellular compartment into the retinal compartment. In effect, the K+ transport of the retinal pigment epithelium depends on the K+ concentration in the retinal compartment in such a way as to keep variations in this concentration at a minimum.

Macular morphology and visual acuity after macular hole surgery with or without internal limiting membrane peeling

Aim: To examine postoperative macular morphology and visual outcome after 12 months in relation to internal limiting membrane (ILM) peeling versus no peeling, indocyanine green (ICG) staining and re-operation in eyes that achieved macular hole closure after surgery. Methods: Seventy-four eyes with closed stage 2 or 3 macular holes were recruited from a randomised clinical trial comparing: (1) vitrectomy without ILM peeling; (2) vitrectomy with 0.05% isotonic ICG-assisted ILM peeling; and (3) vitrectomy with 0.15% trypan blue-assisted ILM peeling. Contrast-enhanced Stratus optical coherence tomography was used to assess central foveal thickness, central photoreceptor layer thickness (CPRT), central photoreceptor layer discontinuity (PRD) and relative reflectivity of the outer nuclear layer. Outcomes were correlated with best corrected visual acuity (BCVA) 12 months after surgery. Results: BCVA was correlated with CPRT and PRD. Regression analysis and receiver operating characteristics curve analysis showed that CPRT >33 μm (OR 12.5) and PRD <177 μm (OR 9.86) were highly predictive for regaining reading vision (⩾69 Early Treatment of Diabetic Retinopathy Study letters) 12 months after surgery. No significant difference was found in postoperative macular morphology between subgroups. Conclusions: Poor vision after 12 months despite macular hole closure was associated with attenuation and disruption of the foveolar photoreceptor matrix. The extent of attenuation and disruption was independent of peeling and staining. Trial registration number: NCT00302328

Subretinal Implantation of Electrospun, Short Nanowire, and Smooth Poly(ε-caprolactone) Scaffolds to the Subretinal Space of Porcine Eyes

Biodegradable scaffolds play an important adjunct role in transplantation of retinal progenitor cells (RPCs) to the subretinal space. Poly(ε-Caprolactone) (PCL) scaffolds with different modifications were subretinally implanted in 28 porcine eyes and evaluated by multifocal electroretinography (mfERG) and histology after 6 weeks of observation. PCL Short Nanowire, PCL Electrospun, and PCL Smooth scaffolds were well tolerated in the subretinal space in pigs and caused no inflammation and limited tissue disruption. PCL Short Nanowire had an average rate of preserved overlying outer retina 17% higher than PCL Electrospun and 25% higher than PCL Smooth. Furthermore, PCL Short Nanowire was found to have the most suitable degree of stiffness for surgical delivery to the subretinal space. The membrane-induced photoreceptor damage could be shown on mfERG, but the reductions in P1 amplitude were only significant for the PCL Smooth. We conclude that of the tested scaffolds, PCL Short Nanowire is the best candidate for subretinal implantation.

Normative data of outer photoreceptor layer thickness obtained by software image enhancing based on Stratus optical coherence tomography images

Aim: To present normative data of outer photoreceptor layer thickness obtained by a new semiautomatic image analysis algorithm operating on contrast-enhanced optical coherence tomography (OCT) images. Methods: Eight Stratus OCT3 scans from identical retinal locations from 25 normal eyes were registered and combined to form a contrast-enhanced average image. Utilising the vertical intensity gradients of the enhanced OCT images to demarcate retinal layers, thickness measurements of the outer photoreceptor- and retinal pigment epithelium layer (RPE-OScomplex) were obtained. Additionally backscattered light within the outer nuclear layer (ONL) in the fovea was registered and compared with backscattered light within the ONL in the peripheral part of the macula (Iratio-ONL). Results: The mean RPE-OScomplex thickness in the foveal centre was 77.2 μm (SD = 3.95). The RPE-OScomplex thickness in the superior macula 0.5–3 mm of the centre was significantly increased as compared with the corresponding inferior retina. In healthy subjects, the Iratio-ONL was 1.06. Conclusions: Contrast-enhanced OCT images enable quantification of outer photoreceptor layer thickness, and normative values may help understanding better the relationship between functional outcome and photoreceptor morphology in retinal diseases.

The mechanism of electrodiffusive K+ transport in leaky epithelia and some of its consequences for anion transport

The ventricular membrane of the epithelium from the choroid plexus ofNecturus maculosus was probed with double-barrelled ion-selective microelectrodes while the ventricular bathing solution was changed abruptly. The transient states induced by increasing the external concentration of K+ or by the application of ouabain showed that the passive movements of K+ across the ventricular membrane were electro-diffusive and could be described by the Goldmann equation and one constant permeability (PK) of 24×10−6 cm s−1. The passive efflux was balanced by a ouabain-sensitive influx.PK was different in different steady states; when the cell was acidified by half a pH unit by increasing CO2 in the bathing solutions from 1 to 5%, thenPK decreased to 13×10−6 cm s−1. Removal of Cl− from the bathing solution increasedPK by 50% and reduction of Cl− transport by furosemide did not alterPK, consequently major movements of K+ were independent of Cl− movements. Depolarizations of the cell caused an increase in the cellular HCO3− concentration due to an electrodiffusive permeability (PHCO3), the value of which was estimated to 17×10−6 cm s−1.

Kinetic properties and Na+ dependence of rheogenic Na(+)-HCO3- co-transport in frog retinal pigment epithelium.

1. Na(+)‐HCO3‐ co‐transport across the retinal membrane of the frog retinal pigment epithelium was studied by means of double‐barrelled pH‐selective microelectrodes. Transient changes in the intracellular pH were monitored in response to abrupt changes in the Na+ concentration on the retinal side of the epithelium. 2. The experiments were performed as follows. The Na(+)‐HCO3‐ co‐transport was inhibited by perfusing the retinal side of the epithelium with a Na(+)‐free solution. The co‐transport was then stimulated by changing the perfusate from the Na(+)‐free solution to a solution which contained from 5 to 110 mM‐Na+. The resulting inward Na(+)‐HCO3‐ co‐transport produced an intracellular alkalinization, the initial rate of which was used to calculate the initial rate of Na(+)‐HCO3‐ co‐transport, JHCO3‐. 3. The Na+ dependence of the Na(+)‐HCO3‐ co‐transport was studied at two different values of extracellular pH (7.40 and 7.10), at constant extracellular HCO3‐ concentration (27.5 mM) and at two different extracellular HCO3‐ concentrations (27.5 mM and 55 mM) at constant extracellular pH (7.40). In these experiments, the calculated values of JHCO3‐ followed single Michaelis‐Menten kinetics with respect to the extracellular Na+ concentration. 4. The data are consistent with a model in which the co‐transporter has a single binding site for the Na+ ion with an apparent affinity constant (apparent Km) of 37 mM. The apparent affinity constant for Na+ was independent of the extracellular concentration of CO3(2‐) in the range of 16‐65 microM, and of the extracellular HCO3‐ concentration in the range 27.5‐55 mM. 5. The NaCO3‐ ion‐pair hypothesis, in which sodium binds to the co‐transporter and is translocated across the cell membrane as the NaCO3‐ ion pair, was analysed. For stoichiometries 1:2 and 1:3 of the Na(+)‐HCO3‐ co‐transport, the NaCO3‐ ion‐pair hypothesis was found incompatible with the data. 6. The intracellular buffer capacity as measured by the CO2 method was 15 mM.