The corneal surface is, without question, the most specialised 123 mm2* of the body's surface. It forms an integral part of the ocular surface with which it shares several anatomical and physiological attributes. Like the rest ofthe body surface, it is in a state of constant 'healing'. Squamous epithelial cells are continually shed into the tear pool and simultaneously replenished by cells moving centrally from the limbus and anteriorly from the basal layers of the epithelium. This concept was propounded by Thoft' in his X, Y, Z hypothesis and is substantiated by several observations and experiments. X represents the proliferation of basal epithelial cells, Y is the proliferation and centripetal migration ofthe limbal cells, and Z the epithelial cell loss from the surface. For a state of equilibrium to be maintained X+Y must equal Z. It is estimated that the corneal epithelium is constantly renewed every 7 to 10 days.2 When this equilibrium is disturbed, as occurs dramatically after an abrasion, the corneal epithelial wound healing response sets in. This is essentially an exaggeration of the normal physiological process involving cellular and subcellular events occurring under the influence of extracellular matrix proteins and growth factors.

https://bjo.bmj.com/content/bjophthalmol/78/5/401.full.pdf

Corneal epithelial wound healing.

Purpose:To evaluate the prevalence of the most common serious adverse events associated with intravitreous (IVT) injection.Methods:A systematic search of the literature via PubMed from 1966 to March 1, 2004, was conducted to identify studies evaluating the safety of IVT injection. Data submitted in

Risks of intravitreous injection: a comprehensive review.

Background
Good unaided distance visual acuity (VA) is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation Near vision, however, still requires additional refractive power, usually in the form of reading glasses Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs

Objectives
To assess the visual effects of multifocal IOLs in comparison with the current standard treatment of monofocal lens implantation

Search methods
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (wwwisrctncom/editAdvancedSearch), ClinicalTrialsgov (wwwclinicaltrialsgov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (wwwwhoint/ictrp/search/en) We did not use any date or language restrictions in the electronic searches for trials We last searched the electronic databases on 13 June 2016

Selection criteria
All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included Both unilateral and bilateral implantation trials were included We also considered trials comparing multifocal IOLs with "monovision" whereby one eye is corrected for distance vision and one eye corrected for near vision

Data collection and analysis
We used standard methodological procedures expected by Cochrane We assessed the 'certainty' of the evidence using GRADE

Main results
We found 20 eligible trials that enrolled 2230 people with data available on 2061 people (3194 eyes) These trials were conducted in Europe (13), China (three), USA (one), Middle East (one), India (one) and one multicentre study in Europe and the USA Most of these trials compared multifocal with monofocal lenses; two trials compared multifocal lenses with monovision There was considerable variety in the make and model of lenses implanted Overall we considered the trials at risk of performance and detection bias because it was difficult to mask participants and outcome assessors It was also difficult to assess the role of reporting bias

There was moderate-certainty evidence that the distance acuity achieved with multifocal lenses was not different to that achieved with monofocal lenses (unaided VA worse than 6/6: pooled RR 096, 95% confidence interval (CI) 089 to 103; eyes = 682; studies = 8) People receiving multifocal lenses may achieve better near vision (RR for unaided near VA worse than J3/J4 was 020, 95% CI 007 to 058; eyes = 782; studies = 8) We judged this to be low-certainty evidence because of risk of bias in the included studies and high heterogeneity (I2 = 93%) although all included studies favoured multifocal lenses with respect to this outcome

People receiving multifocal lenses may be less spectacle dependent (RR 063, 95% CI 055 to 073; eyes = 1000; studies = 10) We judged this to be low-certainty evidence because of risk of bias and evidence of publication bias (skewed funnel plot) There was also high heterogeneity (I2 = 67%) but all studies favoured multifocal lenses We did not additionally downgrade for this

Adverse subjective visual phenomena were more prevalent and more troublesome in participants with a multifocal IOL compared with monofocals (RR for glare 141, 95% CI 103 to 193; eyes = 544; studies = 7, low-certainty evidence and RR for haloes 358, 95% CI 199 to 646; eyes = 662; studies = 7; moderate-certainty evidence)

Two studies compared multifocal lenses with monovision There was no evidence for any important differences in distance VA between the groups (mean difference (MD) 002 logMAR, 95% CI -002 to 006; eyes = 186; studies = 1), unaided intermediate VA (MD 007 logMAR, 95% CI 004 to 010; eyes = 181; studies = 1) and unaided near VA (MD -004, 95% CI -008 to 000; eyes = 186; studies = 1) compared with people receiving monovision People receiving multifocal lenses were less likely to be spectacle dependent (RR 040, 95% CI 030 to 053; eyes = 262; studies = 2) but more likely to report problems with glare (RR 141, 95% CI 114 to 173; eyes = 187; studies = 1) compared with people receiving monovision In one study, the investigators noted that more people in the multifocal group underwent IOL exchange in the first year after surgery (6 participants with multifocal vs 0 participants with monovision)

Authors' conclusions
Multifocal IOLs are effective at improving near vision relative to monofocal IOLs although there is uncertainty as to the size of the effect Whether that improvement outweighs the adverse effects of multifocal IOLs, such as glare and haloes, will vary between people Motivation to achieve spectacle independence is likely to be the deciding factor

/pdf/multifocal-versus-monofocal-intraocular-lenses-after-2ypb97izw2.pdf

Multifocal versus monofocal intraocular lenses after cataract extraction

The ReSTOR intraocular lens presents a unique apodized diffractive design within a refractive foldable acrylic optic, which makes an unprecedented level of mulifocal optical performance available. We describe the history and principles of diffractive optics used in the development of this refractive-diffractive IOL.

History and development of the apodized diffractive intraocular lens.

Multifocal versus monofocal intraocular lenses in cataract surgery: A systematic review

Purpose: To compare intraoperative and postoperative complications in eyes with and without pseudoexfoliation having cataract surgery by phacoemulsification. Setting: Department of Ophthalmology, National Hospital, Oslo, Norway. Methods: Of 1152 consecutive phacoemulsification procedures, 164 cases with pseudoexfoliation (Group 1) and 916 cases without (Group 2) were followed for 4 months after cataract surgery in a prospective study. Of all cataract operations performed during that time, 96.2% were phacoemulsification procedures: 90.4 and 97.4% in eyes with and without pseudoexfoliation, respectively ( P Results: The frequency of capsular/zonular tear or vitreous loss was 9.6 and 3.7% in Groups 1 and 2, respectively ( P = .0002). A visual acuity of 0.5 or better was achieved in 86.5% of eyes in Group 1 and 92.4% in Group 2 ( P = .02). There were no statistically significant between-group differences in the frequency of a postoperative inflammatory response 1 day (6.7 versus 4.4%), 1 week (2.4 versus 1.6%), or 4 months (1.8 versus 0.9%) postoperatively. Conclusion: Phacoemulsification was safe in most eyes with pseudoexfoliation even though significantly more complications occurred intraoperatively in these eyes. The low frequency of an inflammatory response indicates that the presence of pseudoexfoliation does not significantly increase the risk of inflammation.

Phacoemulsification in eyes with pseudoexfoliation

Purpose: To compare a Pharmacia diffractive bifocal intraocular lens (IOL) with a monofocal lens of the same design without the diffractive grating. Setting:. Multicenter study. Methods: This randomized, prospective study comprised 70 patients with a monofocal IOL and 79 with a diffractive bifocal IOL. Follow-up was 5 to 6 months. Near and distance visual acuities, contrast sensitivity, patient satisfaction, and spectacle use were evaluated. Results: All patients achieved a best corrected visual acuity of 0.5 or better; 80% in the monofocal and 71 % in the bifocal group had a best corrected visual acuity of 1.0 or better. Without correction, 93% of the bifocal and 9% of the monofocal group could read J3 or better. With distance correction, 99% and 4%, respectively, could read J3 or better. Contrast sensitivity was slightly lower in the bifocal group at distance and near for all spatial frequencies. In the bifocal group, 46% never used spectacles for near tasks. Overall satisfaction was rated good by 86% of the monofocal and 85% of the bifocal group. Conclusions: The diffractive bifocal IOL performed well at distance and near. Patients who no longer require spectacles will benefit significantly from a bifocal IOL, but many with a bifocal IOL in one eye will require spectacles for the fellow eye.

Comparison of a diffractive bifocal and a monofocal intraocular lens

Purpose To determine the incidence, clinical presentation, etiology, and outcomes of postoperative endophthalmitis in Norway and to explore the potential of and establish a platform for improving diagnostics, prophylaxis, and treatment of postoperative endophthalmitis. Setting All ophthalmic surgical units and relevant microbiology laboratories in Norway. Methods A national registry of cases of postoperative endophthalmitis was established in 1996. All ophthalmic surgery units in Norway were asked to return forms including preoperative, perioperative, and postoperative data for each case of endophthalmitis occurring between January 1996 and December 1998 after any intraocular surgery irrespective of the time between the surgery and the onset of endophthalmitis symptoms. All microbiology laboratories in Norway were asked to return questionnaires regarding their routine handling procedures of eye specimens in cases of endophthalmitis. Results From 1996 to 1998, 111 suspected endophthalmitis cases were reported, all after cataract surgery. Eighty cases were culture positive, 75 with gram-positive bacteria, 4 with gram-negative bacteria, and 1 with Candida albicans . Depending on the definition, the incidence of postoperative endophthalmitis was between 0.11% and 0.16%. Thirteen percent of cases had "delayed" endophthalmitis. Twenty-nine percent of eyes had an outcome of permanent amaurosis or light perception visual acuity; 56% (47/84) retained or improved their categorized visual acuity in the affected eye compared to preoperatively. Positive bacterial growth was associated with a worse visual outcome ( P = .008). The degree of inflammation when endophthalmitis was diagnosed and the visual outcomes were worse in cases with growth of streptococci than in cases with growth of staphylococci ( P = .009 and P Conclusions Postoperative endophthalmitis remains a serious complication of intraocular surgery, although the prognosis depends greatly on the microbe isolated. Common guidelines should be established regarding clinical and microbiological diagnosis and treatment. Further improvement of the registry would make it a suitable platform for evaluating prophylactic treatments.

Postoperative endophthalmitis: establishment and results of a national registry

Purpose: To compare contrast sensitivity (CS) after implantation of a diffractive bifocal intraocular lens (IOL) and a monofocal IOL of similar design. Setting: Seven European centers. Methods: In this randomized, prospective study, CS was tested 5 months after cataract and IOL implantation surgery in 115 patients with a diffractive bifocal IOL and 106 patients with a monofocal IOL. It was also tested in a subgroup of 38 patients who had bilateral implantation of a diffractive bifocal IOL. Contrast sensitivity was tested using the Vision Contrast Test System (VCTS). Results: In patients with a best corrected visual acuity (BCVA) of 1.0 or better, the CS at all spatial frequencies (1.5 to 18 cycles/degree), both at distance and near, was slightly lower in the bifocal IOL group than in the monofocal group. Mean values were within the normal range. In patients with a BCVA of less than 1.0, the CS was lower and the difference between the bifocal and monofocal groups was less. In patients with bilateral bifocal IOLs, CS was better when tested bilaterally than when testing the better eye alone. Pupil size affected the results to a small degree. Contrast sensitivity appeared to improve over time after implantation of a diffractive bifocal IOL. Conclusions: In patients with cataract and no other eye pathology, the diffractive bifocal IOL will slightly reduce the CS at all spatial frequencies. In those with reduced visual acuity after cataract surgery, CS will be reduced accordingly. In this situation, the reduction from the diffractive bifocal optic would be minor.

Contrast sensitivity after implantation of diffractive bifocal and monofocal intraocular lenses

. Rats with small (diam. 1.7 mm), medium sized (diam. 35 mm) or large (diam. 5.5 mm) corneal epithelial erosions in one eye were killed 1,2 or 4 days after the injury. The proliferative response was evaluated by measuring the labelling index and the mitotic rate in the corneal epithelium and in the adjacent conjunctiva. The small erosions triggered a proliferative response in the cornea only with the maximum response occurring midperipherally. The medium sized erosions induced a higher and more extensive response in the cornea and also a slight increase of the labelling index in the limbal area. The large erosions induced an even more pronounced response in the peripheral cornea and an increase both of the labelling index and the mitotic rate well beyond the limbal part of the conjunctiva. It is concluded that the magnitude and the extent both of the conjunctival and the corneal regenerative response to a corneal abrasion is correlated to the size of the corneal defect. Temporary reduction in the conjunctival epithelial cell number shows that both cells in the limbal and the extralimbal conjunctiva migrate centri-petally during healing of large corneal wounds. It is suggested that the stem cell theory should be modified. The limbal area is probably an area in which conjunctival epithelial cells or conjunctiva-derivated cells transform or differentiate to corneal epithelial cells.

Kjell U. Sandvig

Papers

Phacoemulsification in eyes with pseudoexfoliation

Comparison of a diffractive bifocal and a monofocal intraocular lens

Postoperative endophthalmitis: establishment and results of a national registry

Contrast sensitivity after implantation of diffractive bifocal and monofocal intraocular lenses

Cell kinetics of conjunctival and corneal epithelium during regeneration of different-sized corneal epithelial defects.