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Gout ‘more than doubles’ risk of kidney failure, according to University of Limerick-led research study

Patients with gout are at increased risk of chronic kidney disease and kidney failure, according to recent University of Limerick-led research In one of the largest and most detailed studies ever conducted, patients recruited in general practice with a diagnosis of gout were more than twice as likely to develop kidney failure than those without,…

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Irish pain research in focus

Ms Laura O’Connor, Research Co-ordinator (RLA projects), highlights the work of the Centre for Pain Research, based in NUI Galway The Centre for Pain Research (CPR), based in NUI Galway, is an interdisciplinary research centre, which aims to advance the scientific understanding of pain. Co-directors Professors David Finn and Brian McGuire lead the Centre in…

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Insights into rosacea

Global prevalence of rosacea higher than previously thought, study finds

An estimated 5.46 per cent of the population worldwide is affected by rosacea, with predominance at the age of 45-to-60 years, according to a new systematic review and meta-analysis of published data.

No significant difference between men and women and no significant association between higher prevalence and latitude were observed in the study, published in the British Journal of Dermatology this summer.

The authors of the study, a group of researchers of the University of Copenhagen, Denmark, selected 32 studies from three databases, namely PubMed, Embase and Web of Sciences, examining 32 studies of 41 populations and a total of 26,519,836 individuals.

Twenty-two populations were from Europe, three from Africa, four from Asia, nine from North America and three from South America. The pooled proportion of individuals with rosacea was 5.46 per cent in the general population and 2.39 per cent among dermatological outpatients.

A substantial difference was observed between self-reported rosacea (9.71 per cent) and dermatologist-diagnosed (5.53 per cent) rosacea, suggesting a low specificity of questionnaires based on symptoms.

Rosacea affected both women (5.41 per cent) and men (3.9 per cent), and mostly those aged 45-to-60 years.

No significant association was observed between higher prevalence of rosacea and latitude.

Presence of Demodex mite higher in people with rosacea

Patients with rosacea were significantly more likely than controls to have Demodex mite infestation, according to findings from a study published in the Journal of the American Academy of Dermatology.

The evidence-based meta-analysis of the prevalence and degrees of Demodex mite infestation in patients with rosacea included 1,513 patients from 23 case-control studies.

Patients in the rosacea group were more than nine times more likely to have Demodex mites than controls. Density of Demodex mites was also significantly greater in the rosacea group compared with controls.

Subtype analysis results indicated that Demodex mite density was significantly greater in both erythematotelangiectatic rosacea (standardised mean difference = 2.686) and papulopustular rosacea (standardised mean difference = 2.804), compared with controls.

Other key findings indicated that Demodex mites occurred in 70.4 per cent (range 33.3-to-100 per cent) of patients with rosacea and 31.8 per cent (range 3.8-96 per cent) of controls.

In the rosacea group, the mean density of mites was 71 mites/ cm2 (range 1.9-376.8 mites/cm2), while the density was 8.7 mites/cm2 (range 0.06-89.6 mites/cm2) among controls.

Limitations of the study included that the inter-study variability was high, and a causal relationship could not be established by case-control studies.

“Patients with rosacea had significantly higher prevalence and degrees of Demodex mite infestation than did control patients. Demodex mites may play a role in both erythematotelangiectatic rosacea and papulopustular rosacea,” the researchers concluded.

Separately, a recent Indian study found that rosacea was found to be a statistically significant risk factor for Demodex infestation in eyelashes, irrespective of age and sex, with a higher prevalence in papulopustular variety.

The comparative, open, observational, and cross-sectional study included 41 patients diagnosed with rosacea and 41 referents without rosacea diagnosis or ophthalmic alterations. The individuals underwent a slit-lamp examination in which two eyelashes per eyelid were removed with fine forceps.

Of the 41 patients with rosacea, 31 had erythematotelangiectatic rosacea and 10 had papulopustular rosacea.

The presence of Demodex was found in 32 patients: 24 patients with rosacea diagnosis (16 of the erythematotelangiectatic subtype and eight of papulopustular subtype); and eight patients without rosacea or ophthalmic alterations (P ≤0.001).

It is now accepted that the presence of Demodex mites plays an important role in rosacea aetiopathogenesis. Demodex mite treatment may reduce the severity of the disease and slow its progressive nature.

Rosacea linked to a slightly increased risk of dementia

A new study has uncovered an increased risk of dementia —in particular, Alzheimer’s disease — in patients with rosacea. Importantly, the risk was highest in older patients and in patients where rosacea was diagnosed by a hospital dermatologist. The findings are published in the Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society.

Rosacea, a common chronic inflammatory skin disorder, is characterised by elevated expression of certain proteins —including matrix metalloproteinases and antimicrobial peptides — that are also involved in various neurodegenerative disorders, such as Alzheimer’s disease and other forms of dementia.

A team led by Dr Alexander Egeberg, University of Copenhagen, investigated the association between rosacea and dementia in Danish registers. There were 5,591,718 Danish citizens aged ≥18 between 1997 to 2012, including 82,439 patients with rosacea. Individuals were followed until December 31, 2012; migration, a diagnosis of dementia, or death from any cause, whichever came first. A total of 99,040 individuals developed dementia, of whom 29,193 were diagnosed with Alzheimer’s disease. After adjustments for potential confounding factors, patients with rosacea had a 7 per cent increased risk of dementia and a 25 per cent increased risk of Alzheimer’s disease compared with individuals without rosacea. Stratified by sex, women had a 28 per cent increased risk of Alzheimer’s disease and men had a 16 per cent increased risk if they had rosacea. When results were stratified by age at study entry, the risk of Alzheimer’s disease was only significantly increased in individuals ≥60 years (who had a 20 per cent increased risk). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the increased risks of dementia and Alzheimer’s disease were 42 per cent and 92 per cent, respectively.

“A subtype of patients have prominent neurological symptoms, such as burning and stinging pain in the skin, migraines, and neuropsychiatric symptoms, suggesting a link between rosacea and neurological diseases,” explained Dr Egeberg. “Indeed, emerging evidence suggests that rosacea may be linked with neurological disorders, including Parkinson’s disease and now also Alzheimer’s disease. There are certain mechanistic overlaps between rosacea and Alzheimer’s disease that may explain the observed association, albeit the pathogenic links between these conditions are still unclear.”

Further research is warranted to examine whether treating rosacea may also modify patients’ risk of developing dementia, he said.

New standard classification and pathophysiology of rosacea published

A new standard classification and pathophysiology of rosacea has been published in the Journal of the American Academy of Dermatology. Developed by a consensus committee and review panel of 28 rosacea experts worldwide, the updated system is based on the substantial advances in the understanding of rosacea gained through scientific investigations over the last 15 years.

“There has been an explosion of research on rosacea since the first standard classification system appeared in 2002, and that has resulted in a much deeper scientific understanding of this common but once little-known disorder,” said Dr Richard Gallo, Chairman of Dermatology, University of California-San Diego.

“Growing knowledge of rosacea’s pathophysiology has established that a consistent multivariate disease process underlies its various clinical manifestations, which may also potentially be associated with other systemic disorders.”

Although the cause of rosacea remains unknown, researchers have now identified major elements of the disease process that may lead to significant advances in its treatment. Recent studies have shown that the initial redness is likely to be the start of an inflammatory continuum initiated by a combination of neurovascular dysregulation and the innate immune system.

While the original classification system designated the most common groupings of primary and secondary features as subtypes, the committee noted that because rosacea appears to encompass a consistent inflammatory continuum; it now seems appropriate to focus on the individual characteristics (phenotypes) that may result from this disease process.

Observing the respective phenotypes in clinical practice will also encourage consideration of the full range of potential signs and symptoms that may occur in any individual patient, and assessment of severity and the selection of treatment may be more precisely tailored to each individual, the committee believes.

According to the new system, the presence of one of two phenotypes — persistent redness of the facial skin or, less commonly, phymatous changes where the facial skin thickens — is considered diagnostic of rosacea. Additional major cutaneous signs, which often appear with the diagnostic features, include papules and pustules, flushing, telangiectasia and certain ocular manifestations. The presence of two or more major phenotypes independent of the diagnostic features is also considered diagnostic of rosacea. Secondary phenotypes, which must appear with one or more diagnostic or major phenotypes, include burning or stinging, swelling and dry appearance.

Signs suggestive of ocular rosacea include telangiectasias on the eyelid margin and bloodshot eyes, as well as inflammation and growth of fibrous tissue on the eye. Burning, stinging, light sensitivity and the sensation of a foreign object may also occur, as well as conjunctivitis, inflammation of oil glands at the rim of the eyelids (blepharitis) and crusty accumulations at the base of the eyelashes, in addition to others.

“Although rosacea’s various phenotypes may appear in different combinations and at different times, research suggests that all are manifestations of the same underlying disease process, and that rosacea may progress not only in severity but to include additional phenotypes,” Dr Gallo said.

The committee also acknowledged the psychosocial effects of rosacea, noting that multiple patient surveys have documented rosacea’s substantial adverse impact on emotional, social and occupational well-being. They stressed that this should also be an important consideration, and suggested the development of appropriate severity scales to measure this dimension, as well as the need for further research to adequately assess rosacea’s negative effects.

In an accompanying commentary on rosacea comorbidities and future research, the committee summarised the many recent studies that have found associations between rosacea and increased risk for a growing number of potentially serious systemic disorders. These include cardiovascular disease, gastrointestinal disease, neurological and autoimmune diseases and certain cancers. Although causal relationships have not been determined, the committee noted these findings may significantly increase the clinical significance of rosacea as evidence that the disorder may be an outcome of systemic inflammation continues to mount.

In addition to comorbidities, they identified a number of areas where further research may be of particular value. Recent evidence suggests rosacea may appear often in individuals with darker skin types, and the updated standard criteria can be used to determine its prevalence in various ethnicities as well as populations worldwide. In addition, recent studies have found genetic factors that might affect the disease and may also be used to identify potential further comorbidities. Data also suggest that the skin microbiome may play a role.

The committee noted that, as with the original classification of rosacea, the updated standard system is considered provisional and may require modification as the causes and pathogenesis of rosacea become clearer, and its relevance and applicability are tested by investigators and clinicians.

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A case of keratoconus and cataract: Surgical management over three separate eras

Time is a concept understood only by humans apparently. Very few creatures in the animal world have much concept of yesterday or tomorrow. In the medical profession, we certainly understand the concept of time. Time heals. Time left. Time in theatre. Time out. The list goes on.

In the field of ophthalmology, time passes more quickly given the pace of innovation.

I want to share the concept of time and how it changes the management of common conditions over a short period, perhaps 15 years or less.

Take the case of a patient with progressive keratoconus (steepening of the cornea resulting in irregular astigmatism and reduced quality of vision) who also has a cataract that requires surgery. Three eras, within the timeframe of less than 15 years, provide fascinatingly different approaches and outcomes.

Keratoconus treatment: pre-2007

Before 2007 there was no treatment for progressive keratoconus in Ireland until corneal cross-linking (CXL) was introduced in January 2007, the same month that CXL was approved in the EU.

The keratoconus aspect was previously managed either by rigid contact lenses and if the steepening progressed, by means of a corneal transplant. The cataract was removed using phaco-emulsification of the cataract (breaking the natural lens up into small pieces that can be aspirated through a tiny, sutureless incision, using ultrasound) and replacing it with an intraocular lens (IOL). A challenge in this case would also be the calculation of the IOL power required. When replacing the natural lens, the surgeon has it within his or her power, to select an IOL of the appropriate power to improve the patient’s vision without the use of spectacles. IOL power calculation is notoriously difficult, even today, in these aberrated corneas and getting the IOL power right was a particularly difficult issue.

Furthermore, the diagnosis was very much a clinical diagnosis and there was not much objective validation of the corneal contribution versus the lens contribution to the reduced vision.

Keratoconus treatment: 2007 to present day

From 2007 to the present day CXL has changed the way that we manage keratoconus completely. Back in 1994, I was doing more than 50 corneal transplants per year, that number now is so small, that I no longer do corneal grafts. I refer them to someone that is still doing a reasonable number. This is all thanks to CXL. This procedure strengthens the cornea and, in some cases, even improves the corneal shape thereby improving the quality of vision. CXL was traditionally performed by removing the corneal epithelium, hence leading to a healing phase of the epithelium. For the past six years we are performing 90 per cent of our CXL procedures without removing the corneal epithelium, making the procedure safer, allowing less time off work with much less morbidity.

Combining the procedure with topography-guided photo-refractive keratectomy (TG-PRK) has also allowed the regularisation of the cornea before the improved corneal shape is stabilised by the CXL. This leads to improved corneal optics and simpler and more accurate IOL power calculations for the IOL to be selected. The only IOL in these aberrated corneas that could be contemplated was a monofocal (single focal power) IOL. More recently, we are implanting pinhole optic IOLs (the IC-8 IOL from AcuFocus) in these eyes and the results are outstanding, with the pinhole reducing much of the corneal higher order aberrations that lead to starburst, halos and glare. The pinhole IOL is also more forgiving in terms of refractive accuracy due to the increased depth of focus provided by the pinhole.


Patient undergoing CXL treatment

The diagnosis has become more objective too with devices like the iTrace and the HD Analyzer being able to illustrate the optical contribution from the cornea and from the cataract, making it simpler to plan surgery. Should the cataract be treated first, or should the cornea be treated first? Could they be treated at the same surgical procedure?

Today and the near future

Corneal regularisation may soon be achieved by tissue addition rather than tissue subtraction as we currently do (excimer laser ablation by means of photo refractive keratectomy (PRK)). Allotex Ltd is a company providing excimer laser shaped human corneal lenticules for refractive use. This allows tissue with 0.25-micron accuracy to be used for corneal addition procedures. Clinical trials, expected to commence in Q3 of this year in eight European sites including the Wellington Eye Clinic in Dublin for presbyopia and hyperopia, are expected to prove the value of this technique for regular corneas and lay the foundation for the use of allograft onlays and inlays for keratoconic corneas. As corneal surgeons, adding thickness to a keratoconic cornea resonates well. With improved corneal regularity, IOL power calculations become more predictable.

However, with keratoconus the posterior corneal surface can also be distorted and current IOL power formulae do not account for this. Refractive surprises are therefore not uncommon. This is where the RxSight Light Adjustable Lens (RxLAL) may play a significant role in improving outcomes. We are currently enrolling eyes in a four-site European study on using this IOL that can be adjusted using UV light after it has been implanted in the eye and allowed time to settle into its final effective lens position (ELP). ELP has always been blamed for missing refractive targets as we have found it challenging to predict the healing and contraction of the capsular bag and its effect on the final IOL position within the eye. With the RxLAL, this no longer matters. Once the IOL has stabilised within the eye, the IOL power is adjusted using a light delivery device (LDD) that can change the power of the IOL to achieve a desired refractive outcome. Incredibly, early results show the accuracy and predictability even supersede that of LASIK. The IOL power can be adjusted up to three times and then ‘locked-in’ with a final treatment after which no further adjustments can occur.


This case study shows how in the relatively short time-frame, that something regarded as radical and innovative only 11 years ago, has evolved in a short time to be potentially replaced by fundamentally different approaches that have led to increased safety, increased predictability and ultimately, increased patient satisfaction.

In the interests of brevity certain further innovations were deliberately omitted, but it is worthwhile mentioning that femtosecond laser innovation is set to further disrupt the current cataract techniques where phaco is used. Within the next 12 months we are commencing a clinical trial where phaco is no longer required following femtosecond laser fragmentation of the cataract.

New drugs are in the pipeline whereby retinal dosages of some pharmacologic agents can be achieved with topical application of drops rather than intravitreal injections.

Innovation is alive and well and ophthalmology has proven to be a fitting partner for our engineering and physics PhD colleagues to apply their considerable talents. It would be wonderful, however, if time could slow down just a tad.

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