Chi Ho To

The mechanism of aqueous humour formation

Aqueous humour (AH) is an important intraocular fluid responsible for the supply of nutrients to and removal of metabolic wastes from the avascular tissues of the eye. It is also indispensable for the maintenance of the optical properties of the eye. The fluid dynamics of AH are frequently associated with the potentially blinding disease called glaucoma. Pharmacological treatment of glaucoma generally aims to lower the intraocular pressure by reducing AH formation. However, the mechanism underlying the formation of AH is still not well understood. Understanding the mechanism of AH formation and its regulation is paramount to develop rational and target specific drugs for the treatment of glaucoma. It is now generally believed that AH is formed mostly by active transport of ions and solutes across the ciliary epithelium. Many studies have been carried out in the past half a century to understand these transport processes. In the past several years, new information has emerged and a comprehensive review of these new developments is necessary. This review covers the ion transports in the ciliary epithelium, including the possible roles of sodium, chloride and bicarbonate ions as the driving forces. It also examines the current ionic models for AH formation and its regulation from a cellular transport perspective.

Defocus Incorporated Soft Contact (DISC) lens slows myopia progression in Hong Kong Chinese schoolchildren: a 2-year randomised clinical trial

Aims To determine if ‘Defocus Incorporated Soft Contact’ (DISC) lens wear slows childhood myopia progression. Methods A 2-year double-blind randomised controlled trial was carried out in 221 children aged 8–13u2005years, with myopia between −1.00 and −5.00 Dioptres (D) and astigmatism ≤1.00u2005D. Subjects were randomly assigned to the DISC (n=111) or single vision (SV; n=110) contact lens group. DISC lenses incorporated concentric rings, which provided an addition of +2.50u2005D, alternating with the normal distance correction. Refractive error (cycloplegic autorefraction) and axial length were measured at 6-month intervals. Differences between groups were analysed using unpaired t test. Results In total, 128 children completed the study, n=65 in the DISC group and n=63 in the SV group. Myopia progressed 25% more slowly for children in the DISC group compared with those in the control group (0.30u2005D/year; 95% CI −0.71 to −0.47 vs 0.4u2005D/year; 95% CI −0.93 to −0.65, p=0.031). Likewise, there was less axial elongation for children in the DISC versus SV groups (0.13u2005mm/year; 95% CI 0.20 to 0.31 vs 0.18u2005mm/year; 95% CI 0.30 to 0.43, p=0.009). Treatment effect correlated positively with DISC lens wearing time (r=0.342; p=0.005). Indeed, myopia in children who wore the DISC lenses for five or more hours/day progressed 46% (mean difference=−0.382u2005D, p=0.001; 95% CI −0.59 to −0.17) less than those in the SV group. Conclusions The daily wearing of DISC lens significantly slowed myopia progression and axial elongation in Hong Kong schoolchildren. The findings demonstrated that simultaneous clear vision with constant myopic defocus can retard myopia progression.

Differences in the Corneal Biomechanical Changes After SMILE and LASIK

PURPOSEnTo compare the corneal biomechanical properties before and after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK in different levels of myopia with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Depew, NY).nnnMETHODSnA total of 187 and 79 eyes that received SMILE or LASIK, respectively, between January and June 2013 at Zhongshan Ophthalmic Center were enrolled in this study. Patients were grouped according to surgery type (SMILE or LASIK) and -6.00 diopters (D) or less (> -6.00 D) or myopia greater than -6.00 D (>-6.00 D). Corneal hysteresis, corneal resistance factor, and 37 waveform parameters were recorded and compared preoperatively and at 1 week and 1 and 3 months postoperatively.nnnRESULTSnThere was a significant decrease of corneal hysteresis, corneal resistance factor, p1area, and p2area, and an increase of path1 and path2 in both SMILE and LASIK. In myopia -6.00 D or less, the differences between SMILE and LASIK were not significant (P > .05), but in myopia greater than -6.00 D, the corneal hysteresis, corneal resistance factor, p1area, and p2area decreased significantly more in LASIK than in SMILE (P < .05).nnnCONCLUSIONSnWhen comparing SMILE with LASIK, myopia was greater than -6.00 D, and the corneal hysteresis, corneal resistance factor, p1area, and p2area decrease was less after SMILE.

Cyclic GMP, sodium nitroprusside and sodium azide reduce aqueous humour formation in the isolated arterially perfused pig eye

1 The effect of nitric oxide (NO) on aqueous humour formation (AHF) and intraocular pressure (IOP) was studied using NO donors, sodium azide (AZ) and sodium nitroprusside (SNP). 2 Using the porcine arterially perfused eye preparation, drug effects on AHF and IOP were measured by fluorescein dilution and manometry, respectively. Perfusion pressure of the ocular vasculature was also monitored using digital pressure transducer and pen recorder. 3 L‐Arginine (1.0u2003mM), a precursor of NO, but not D‐arginine (1.0u2003mM), the inactive analogue, produced a significant reduction in AHF (28.5%) and IOP (21.1%). L‐NAME (L‐nitro‐L‐arginine) (10–100u2003μM), an NO synthase inhibitor, had no effect on AHF and IOP. However, L‐NAME (100u2003μM) completely reversed L‐arginines effect. 4 AZ and SNP reduced the AHF and IOP dose‐dependently. AZ at 100u2003nM, 1 and 10u2003μM reduced AHF by 26.0, 39.7 and 51.7% and IOP by 10.8, 17.3 and 24.0%, respectively. SNP at 1, 10 and 100u2003μM reduced the AHF by 6.0, 24.2 and 35.4% and IOP by 3.5, 9.5 and 15.5%, respectively. 8‐pCPT‐cGMP (8‐para‐chlorophenyl‐thioguanosine‐3′,5′‐cyclic guanosine monophosphate, 10u2003μM), a cGMP analogue, also reduced the AHF (34.9%) and IOP (15.9%). 5 The effects of AZ and SNP on the AHF and IOP were blocked by a soluble guanylate cyclase inhibitor ODQ (10u2003μM), whereas ODQ alone or combined with 8‐pCPT‐cGMP had no effect on the AHF and IOP. 6 None of the drugs had any significant effect on ocular vasculature. 7 The reduction of the AHF and IOP in the arterially perfused pig eye by nitrovasodilators is likely to involve the NO‐cGMP pathway.

Axes of astigmatism in fellow eyes show mirror rather than direct symmetry

Purpose:u2002 Most astigmats have a similar level of astigmatism in each eye. However, there is controversy over whether the astigmatic axes in fellow eyes typically show direct or mirror symmetry. We carried out a statistical analysis designed to address this issue.

Characterisation of Cl⁻ transporter and channels in experimentally induced myopic chick eyes.

Background:u2002 Experimental evidence has shown that myopic and hyperopic optical defocus induces thickening and thinning of the choroids, respectively, moving the retina forward and backward toward the plane of focus; however, the underlying mechanism of this phenomenon remains elusive. It has been hypothesised that the change in choroidal thickness might be elicited by the alteration of ion and fluid transport across the retinal pigment epithelium (RPE). Therefore, the aims of the present study were to determine the content of specific Cl‐ transporter/channel mRNA and proteins in chick RPE in a normal, untreated state and in lens‐induced myopia.

Studies on bicarbonate transporters and carbonic anhydrase in porcine nonpigmented ciliary epithelium.

PURPOSEnBicarbonate transport plays a role in aqueous humor (AH) secretion. The authors examined bicarbonate transport mechanisms and carbonic anhydrase (CA) in porcine nonpigmented ciliary epithelium (NPE).nnnMETHODSnCytoplasmic pH (pH(i)) was measured in cultured porcine NPE loaded with BCECF. Anion exchanger (AE), sodium bicarbonate cotransporter (NBC), and CA were examined by RT-PCR and immunolocalization. AH secretion was measured in the intact porcine eye using a fluorescein dilution technique.nnnRESULTSnAnion exchanger AE2, CAII, and CAIV were abundant in the NPE layer. In cultured NPE superfused with a CO(2)/HCO(3)(-)-free HEPES buffer, exposure to a CO(2)/HCO(3)(-)-containing buffer caused rapid acidification followed by a gradual increase in pH(i). Subsequent removal of CO(2)/HCO(3)(-) with HEPES buffer caused rapid alkalinization followed by a gradual decrease in pH(i). The rate of gradual alkalinization after the addition of HCO(3)(-)/CO(2) was inhibited by sodium-free conditions, DIDS, and the CA inhibitors acetazolamide and methazolamide but not by the Na-H exchange inhibitor dimethylamiloride or low-chloride buffer. The phase of gradual acidification after removal of HCO(3)(-)/CO(2) was inhibited by DIDS, acetazolamide, methazolamide, and low-chloride buffer. DIDS reduced baseline pH(i). In the intact eye, DIDS and acetazolamide reduced AH secretion by 25% and 44%, respectively.nnnCONCLUSIONSnThe results suggest the NPE uses a Na(+)-HCO(3)(-) cotransporter to import bicarbonate and a Cl(-)/HCO(3)(-) exchanger to export bicarbonate. CA influences the rate of bicarbonate transport. AE2, CAII, and CAIV are enriched in the NPE layer of the ciliary body, and their coordinated function may contribute to AH secretion by effecting bicarbonate transport into the eye.

Sex, Eye Size, and the Rate of Myopic Eye Growth Due to Form Deprivation in Outbred White Leghorn Chickens

PURPOSEnThere is considerable variation in the degree of form-deprivation myopia (FDM) induced in chickens by a uniform treatment regimen. Sex and pretreatment eye size have been found to be predictive of the rate of FD-induced eye growth. Therefore, this study was undertaken to test whether the greater rate of myopic eye growth in males is a consequence of their larger eyes or of some other aspect of their sex.nnnMETHODSnMonocular FDM was induced in 4-day-old White Leghorn chicks for 4 days. Changes in ocular component dimensions and refractive error were assessed by A-scan ultrasonography and retinoscopy, respectively. Sex identification of chicks was performed by DNA test. Relationships between traits were assessed by multiple regression.nnnRESULTSnFD produced (mean +/- SD) 13.47 +/- 3.12 D of myopia and 0.47 +/- 0.14 mm of vitreous chamber elongation. The level of induced myopia was not significantly different between the sexes, but the males had larger eyes initially and showed greater myopic eye growth than did the females. In multiple linear regression analysis, the partial correlation between sex and the degree of induced eye growth remained significant (P = 0.008) after adjustment for eye size, whereas the partial correlation between initial eye size and the degree of induced eye growth was no longer significant after adjustment for sex (P = 0.11). After adjustment for other factors, the chicks sex accounted for 6.4% of the variation in FD-induced vitreous chamber elongation.nnnCONCLUSIONSnThe sex of the chick influences the rate of experimentally induced myopic eye growth, independent of its effects on eye size.

Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren

The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8–16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia.

Multifocal electroretinography in isolated arterially perfused bovine eye

Aim:u2002 To develop an isolated arterially perfused bovine eye as an in vitro model for studying retinal electrophysiology using multifocal electroretinography (mfERG).