A 3-year study on the effect of RGP contact lenses on myopic children.

AIM AND BACKGROUND: Recent studies in the West have shown that rigid gas-permeable (RGP) contact lenses can control the progress of myopia in children. These studies were done on Caucasian children, whose myopias are less rapidly progressive than those which we see in Singaporean children. This three-year study was started in 1993, with the following objectives: 1. To verify whether RGP contact lenses can control the progress of myopia in Singaporean children. 2. If so, to investigate the mechanism by which the lenses control myopia; whether by corneal flattening or by reducing the growth of the axial length. 3. If so, to assess if the effects are permanent, by discontinuing lens wear. MATERIALS AND METHODS: The study was carried out at the Eye Clinic of the School Health Service. Enough school children were referred to the clinic from the various schools to achieve about 100 children wearing contact lenses. Past studies showed that the drop-out rate would be 50%, as there is no cosmetic motivation in 10 year-old children to wear contact lenses. The successful wearers were those who had parental encouragement and support. RESULTS: The results show that there was a suppression of the progress of myopia in children wearing the lenses as compared to their counterparts wearing spectacles. However, only in ten eyes was there arrest of the myopia. For the lenses to be effective, they needed to be worn regularly for about eight hours a day. Reasons for the drop-outs included lack of motivation, lens intolerance and simply being too busy with the school curriculum. Discontinuance of lens wear for more than 2 months had minimal effect on the refraction, indicating that the controlling effect was not due purely to corneal change. CONCLUSION: It is recommended that more studies be done to confirm the findings of this study. Children with rapidly progressive myopia can wear rigid gas-permeable contact lenses to reduce the progression.

The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts.

BACKGROUND: A complex of MCM proteins is implicated in ensuring that DNA replicates only once in each cell cycle, by 'replication licensing'. The nuclear membrane is also implicated in replication licensing, but the relationship between the MCM proteins and the nuclear membrane is unclear. Here, we investigate the relationship between XMCM3 (a component of the Xenopus MCM complex), nuclear envelope permeability and the initiation of DNA replication once per cell cycle. RESULTS: Our results show that the nuclear envelope does not prevent the entry of XMCM3 into the nucleus, but that it does prevent the binding of XMCM3 to chromatin. We have also identified another component of the Xenopus MCM complex as a homologue of the Schizosaccharomyces pombe protein Cdc21. XMCM3 does not preferentially co-localize with sites of DNA replication. Instead, it is almost uniformly distributed on chromatin and is suddenly lost during replication. XMCM3 crosses intact nuclear membranes of G2-phase HeLa cells but cannot then bind to chromatin. Permeabilization of the nuclear envelope allows the binding of XMCM3 to G2-phase chromatin. We have therefore resolved replication licensing into two stages. The first requires the entry of a cytosolic 'loading factor' that is excluded by the nuclear membrane; subsequently, MCM3 can bind to chromatin in the presence or absence of a nuclear membrane, but only if the loading factor has gained access in the absence of the membrane. CONCLUSIONS: The Xenopus MCM complex contains homologues of yeast MCM2, MCM3, MCM5 and Cdc21 proteins. XMCM3 is displaced from chromatin during replication. The nuclear envelope allows entry of XMCM3 into the nucleus, but regulates its binding to chromatin; binding requires a loading factor which cannot cross the nuclear envelope. Based on these results we present a two-stage model for replication licensing.

Purification of an MCM-containing complex as a component of the DNA replication licensing system.

Replication licensing factor (RLF) ensures that eukaryotic chromosomal DNA is replicated exactly once in each cell cycle. On exit from metaphase, RLF is activated and binds to or modifies chromatin. This modification (the 'licence') is required for subsequent DNA replication; the licence is also inactivated in the process of replication. Active RLF is not imported into the nucleus, so further DNA replication cannot occur until the DNA is relicensed by passage throught mitosis. We have developed an assay to purify RLF from Xenopus eggs. Activity resolves into two components, RLF-M and RLF-B, both of which are required for licensing. RLF-M has been purified to apparent homogeneity: it consists of three polypeptides, one of which is a Xenopus homologue of the yeast MCM3 protein. Xenopus Mcm3 associates with chomatin in G1 and is removed during replication, consistent with its being a component of the RLF system.

MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells.

An intact nuclear membrane restricts DNA replication to only one round in each cell cycle, apparently by excluding an essential replication-licensing factor throughout interphase. A family of related yeast replication proteins, MCM2, 3 and 5 (also called, after cell-division cycle, CDC46), resemble licensing factor, entering the nucleus only during mitosis. We have cloned a Xenopus homologue of MCM3 (XMCM3) and raised antibodies against expressed protein. Immunodepletion of Xenopus egg extracts removes a complex of MCM2, 3 and 5 homologues and inhibits replication of Xenopus sperm nuclei or permeable G2 HeLa nuclei. However, G1 HeLa nuclei still replicate efficiently. Mock-depleted extracts replicate all three templates. XMCM3 accumulates in nuclei before replication but anti-XMCM3 staining decreases during replication. These results can explain why replicated nuclei are unable to reinitiate replication in a single cell cycle.

Can contact lenses control the progression of myopia?

Myopia is a potentially blinding condition with serious socio-economic ramifications. Many causes have been alluded to and one of the strongest associations is that of formal education and nearwork. Studies done both locally and abroad illustrate this. In addition, Singaporeans were found to have one of the highest incidences of myopia in the world. Many methods, including the use of contact lenses, have been advocated in the control of myopia. Hard contact lenses and more recently, rigid gas permeable lenses, have been studied both to arrest the progression of myopia in the young and reduce existing myopia (by orthokeratology) in the Caucasian population. However, the Asian eye differs from the Caucasian eye. This is evidenced by the increased frequency and severity of myopia, and the difference in the pattern of corneal diseases in our population. As such, there is a need for local studies to be conducted to assess the effectiveness of this method in our population.

Spontaneous hematic cysts of the orbit presenting with acute proptosis. A report of three cases.

Three cases of spontaneous hematic cyst of the orbit are described. All cases presented with acute onset of proptosis, conjunctival chemosis, choroidal folds, restricted ocular movement, and optic nerve compression syndrome with very poor vision. A computed tomography scan demonstrated a cystic lesion situated in the upper part of the orbit. Exploration revealed a cyst containing chocolate-colored fluid. Visual recovery was complete in two of three cases. There was no definite history of trauma in all three cases. Chronic hematic cysts have been described recently, but cases with acute onset such as ours have not to our knowledge been described clearly.

Corneal blindness in Singapore and its prevention.

The pattern of corneal disorders in Singapore is different from that seen in the western countries, and in the developing countries. Dendritic corneal ulceration, keratoconus and corneal dystrophy are relatively uncommon. Bullous Keratopathy, however, is on the increase, due mainly to the increasing number of cataract operations done and to the use of intraocular implants. Other major corneal disorders in Singapore are Exposure Keratitis and Neurotrophic Keratitis. The management of the various corneal disorders are discussed. Prevention is possible especially in those disorders due to iatrogenic factors. Constant vigilance and care are called for to prevent unnecessary surgical trauma and corneal blindness.

Eye diseases in the elderly in Singapore.

Ocular disorders in the elderly have become more important because of increased longevity and the demand for good vision. Many serious ocular conditions are age-related and they include cataract, glaucoma, diabetic retinopathy and other retinal conditions. The most important ocular disorder is cataract which fortunately is curable with excellent results when a posterior chamber implant is inserted. Angle closure glaucoma is common in the elderly Singapore Chinese and can be effectively treated with microscopic peripheral iridectomy or trabeculectomy. Blindness from diabetic retinopathy can be prevented with argon laser photocoagulation. In most cases blindness is preventable with early diagnosis e.g. in glaucoma and diabetic retinopathy. Severe visual loss in the elderly requires careful explanation and compassion by doctors and social workers.

Argon laser photocoagulation in diabetic retinopathy: five year review of 697 treated eyes.

Diabetic retinopathy has now become a common cause of blindness in Singapore. Fortunately, laser photocoagulation has prevented blindness in the majority of patients who were treated. An analysis of 872 patients treated with argon laser photocoagulation showed that 424 patients (48.6%) were for diabetic retinopathy. Patients with adequate treatment retained useful vision. Those who lost vision frequently had associated target organ involvement besides inadequate laser treatment. Patients with proliferative diabetic retinopathy were treated with peripheral retinal photocoagulation. Patients with diabetic maculopathy especially those with focal leaks were treated with localised photocoagulation. A common cause of blindness is failure to recognise the condition early. Physicians and general practitioners must, in the management of diabetics, examine their patients periodically with the pupils dilated in a darkened room.