Multispectral imaging of the ocular fundus using light emitting diode illumination

We present an imaging system based on light emitting diode (LED) illumination that produces multispectral optical images of the human ocular fundus. It uses a conventional fundus camera equipped with a high power LED light source and a highly sensitive electron-multiplying charge coupled device camera. It is able to take pictures at a series of wavelengths in rapid succession at short exposure times, thereby eliminating the image shift introduced by natural eye movements (saccades). In contrast with snapshot systems the images retain full spatial resolution. The system is not suitable for applications where the full spectral resolution is required as it uses discrete wavebands for illumination. This is not a problem in retinal imaging where the use of selected wavelengths is common. The modular nature of the light source allows new wavelengths to be introduced easily and at low cost. The use of wavelength-specific LEDs as a source is preferable to white light illumination and subsequent filtering of the remitted light as it minimizes the total light exposure of the subject. The system is controlled via a graphical user interface that enables flexible control of intensity, duration, and sequencing of sources in synchrony with the camera. Our initial experiments indicate that the system can acquire multispectral image sequences of the human retina at exposure times of 0.05 s in the range of 500-620 nm with mean signal to noise ratio of 17 dB (min 11, std 4.5), making it suitable for quantitative analysis with application to the diagnosis and screening of eye diseases such as diabetic retinopathy and age-related macular degeneration.

Use of Google as a tool to aid diagnosis by optometry students

Background: Previous work has shown that medical problems can be diagnosed by practitioners using Google. The aim of this study was to determine whether optometry students would benefit from using Google when diagnosing eye diseases. Methods: Participants were given symptoms and signs and instructed to list three key words and use them to search Aston University e-Library and Google UK. Results: Aston University e-Library only search resulted in correct diagnosis in 16 of 60 simulated cases. Aston e-Library plus Google search resulted in correct diagnosis in 31 of 60 simulated cases. Conclusion: Google is a useful aid to help optometry students improve their success rate when diagnosing eye conditions.

Minimally invasive microneedles for ocular drug delivery

Introduction: Anterior and posterior segment eye diseases are highly challenging to treat, due to the barrier properties and relative inaccessibility of the ocular tissues. Topical eye drops and systemically delivered treatments result in low bioavailability. Alternatively, direct injection of medication into the ocular tissues is clinically employed to overcome the barrier properties, but injections cause significant tissue damage and are associated with a number of untoward side effects and poor patient compliance. Microneedles (MNs) has been recently introduced as a minimally invasive means for localizing drug formulation within the target ocular tissues with greater precision and accuracy than the hypodermic needles.  Areas covered: This review article seeks to provide an overview of a range of challenges that are often faced to achieve efficient ocular drug levels within targeted tissue(s) of the eye. It also describes the problems encountered using conventional hypodermic needle-based ocular injections for anterior and posterior segment drug delivery. It discusses research carried out in the field of MNs, to date.
Expert opinion: MNs can aid in localization of drug delivery systems within the selected ocular tissue. And, hold the potential to revolutionize the way drug formulations are administered to the eye. However, the current limitations and challenges of MNs application warrant further research in this field to enable its widespread clinical application.  

Prevalence of biomicroscopic findings in the anterior segment and ocular adnexa among schoolchildren in Natal/Brazil

Objective: To determine the prevalence of ocular findings of the external structures and anterior segment of the eye, detected by biomicroscopic examination in schoolchildren in Natal (RN) - Brazil. Methods: After previous random selection, 1,024 pupils from elementary and secondary public and private schools in the city of Natal were evaluated from March to June 2001. All were submitted to preestablished standard research norms, consisting of identification, demographic information, ophthalmologic biomicroscopic examination, with slit lamp, performed by ophthalmologists from the “Onofre Lopes” University Hospital. Results: Alterations of the conjunctival and palpebral conditions were the most prevalent (10.4% and 6.2% respectively). Follicles (4.2%) and papillae (3.0%) were the frequent conjunctival lesions, while blepharitis (3.5%) and meibomitis (1.1%) were the most detected abnormalities in the eyelids. Upon examining the cornea, iris, lens and anterior vitreous, the most encountered findings were nubecula (0.5%), papillary membrane reliquiae (0.5%), posterior capsula opacity (0.8%) and hyaloid arteria reliquiae (2.0%). Conclusion: The most prevalent findings affecting the external structures of the eye such as eyelids and conjunctiva, consisted of blepharitis followed by follicular reaction of the conjunctiva. The most prevalent abnormalities in the cornea, iris, lens and anterior vitreous were nubecula, papillary membrane reliquiae, posterior capsular opacity and hyaloid arteria reliquiae, in that order

Ophthalmic findings in albinism

Purpose: Albinism is a rare genetic disorder of melanin production, which can affect only eyes or simultaneously eyes and skin/hair, resulting respectively in ocular (OA) or oculocutaneous albinism (OCA). Through of a case report of a child with OCA we pretend review ophthalmological manifestations of albinism. Case Report: A girl of West African descent was referenced to our appointment for ophthalmological evaluation of oculocutaneous albinism. Visual acuity was 20/310 OD e 20/630 OS by teller cards. In biomicroscopy, iris hypopigmentation and transillumination was visible, allowing to see spiral vessels and other iris details. Fundoscopy showed a denser and complex choroidal circulation due to lack of pigment in retinal pigment epithelium. Foveal hypoplasia was assumed because foveal pit is not apparent and vessels become less respectful of normal arcade and transverse the macula. Results: Melanin plays an important role in the development of the optic system and it’s absence leads to diverse ocular manifestations, such as: iris hypopigmentation and transillumination , reducted pigmentation of retinal pigment epithelium cells, photoreceptor rod cell deficits, foveal hypoplasia, optic nerve hypoplasia and misrouting of optic nerve at the chiasm, with temporal retina fibers inappropriately routed contralaterally instead of ipsilaterally. Photophobia, nystagmus, reduced visual acuity, color impairment and strabismus are other manifestations usually seen in albinism. Conclusion: Ophthalmologists must be familiar with the specific visual manifestations and needs of these patients. It is essential to correct refractive error to optimize visual acuity. Patients should also be advised to wear tinted glasses and sunblock. In more severely affected children they may benefit of low vision consultation and specialized low vision aids like telescopes.

Prevalence of biomicroscopic findings in the anterior segment and ocular adnexa among schoolchildren in Natal/Brazil

Objective: To determine the prevalence of ocular findings of the external structures and anterior segment of the eye, detected by biomicroscopic examination in schoolchildren in Natal (RN) - Brazil. Methods: After previous random selection, 1,024 pupils from elementary and secondary public and private schools in the city of Natal were evaluated from March to June 2001. All were submitted to preestablished standard research norms, consisting of identification, demographic information, ophthalmologic biomicroscopic examination, with slit lamp, performed by ophthalmologists from the “Onofre Lopes” University Hospital. Results: Alterations of the conjunctival and palpebral conditions were the most prevalent (10.4% and 6.2% respectively). Follicles (4.2%) and papillae (3.0%) were the frequent conjunctival lesions, while blepharitis (3.5%) and meibomitis (1.1%) were the most detected abnormalities in the eyelids. Upon examining the cornea, iris, lens and anterior vitreous, the most encountered findings were nubecula (0.5%), papillary membrane reliquiae (0.5%), posterior capsula opacity (0.8%) and hyaloid arteria reliquiae (2.0%). Conclusion: The most prevalent findings affecting the external structures of the eye such as eyelids and conjunctiva, consisted of blepharitis followed by follicular reaction of the conjunctiva. The most prevalent abnormalities in the cornea, iris, lens and anterior vitreous were nubecula, papillary membrane reliquiae, posterior capsular opacity and hyaloid arteria reliquiae, in that order

Automatic Counting of Microglial Cells in Healthy and Glaucomatous Mouse Retinas

Proliferation of microglial cells has been considered a sign of glial activation and a hallmark of ongoing neurodegenerative diseases. Microglia activation is analyzed in animal models of different eye diseases. Numerous retinal samples are required for each of these studies to obtain relevant data of statistical significance. Because manual quantification of microglial cells is time consuming, the aim of this study was develop an algorithm for automatic identification of retinal microglia. Two groups of adult male Swiss mice were used: age-matched controls (naïve, n = 6) and mice subjected to unilateral laser-induced ocular hypertension (lasered; n = 9). In the latter group, both hypertensive eyes and contralateral untreated retinas were analyzed. Retinal whole mounts were immunostained with anti Iba-1 for detecting microglial cell populations. A new algorithm was developed in MATLAB for microglial quantification; it enabled the quantification of microglial cells in the inner and outer plexiform layers and evaluates the area of the retina occupied by Iba-1+ microglia in the nerve fiber-ganglion cell layer. The automatic method was applied to a set of 6,000 images. To validate the algorithm, mouse retinas were evaluated both manually and computationally; the program correctly assessed the number of cells (Pearson correlation R = 0.94 and R = 0.98 for the inner and outer plexiform layers respectively). Statistically significant differences in glial cell number were found between naïve, lasered eyes and contralateral eyes (P<0.05, naïve versus contralateral eyes; P<0.001, naïve versus lasered eyes and contralateral versus lasered eyes). The algorithm developed is a reliable and fast tool that can evaluate the number of microglial cells in naïve mouse retinas and in retinas exhibiting proliferation. The implementation of this new automatic method can enable faster quantification of microglial cells in retinal pathologies.

May's Manual of the diseases of the eye for students and general practitioners.

Includes index.

A treatise on the diseases of the eye.

Bibliographical footnotes.

Hand-book of diseases of the eye : a text-book for students and practitioners /

Mode of access: Internet.

The Norfolk Island Eye Study (NIES) : rationale, methodology and distribution of ocular biometry (Biometry of the Bounty)

Aim: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. Methods: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. Results: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. Conclusion: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease

Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of the retinal dystrophy genes still await discovery. In this thesis we aimed to study the genetic background of two inherited retinal diseases, X-linked cone-rod dystrophy and Åland Island eye disease. X-linked cone-rod dystrophy (CORDX) is characterized by progressive loss of visual function in school age or early adulthood. Affected males show reduced visual acuity, photophobia, myopia, color vision defects, central scotomas, and variable changes in fundus. The disease is genetically heterogeneous and two disease loci, CORDX1 and CORDX2, were known prior to the present thesis work. CORDX1, located on Xp21.1-11.4, is caused by mutations in the RPGR gene. CORDX2 is located on Xq27-28 but the causative gene is still unknown. Åland Island eye disease (AIED), originally described in a family living in Åland Islands, is a congenital retinal disease characterized by decreased visual acuity, fundus hypopigmentation, nystagmus, astigmatism, red color vision defect, myopia, and defective night vision. AIED shares similarities with another retinal disease, congenital stationary night blindness (CSNB2). Mutations in the L-type calcium channel α1F-subunit gene, CACNA1F, are known to cause CSNB2, as well as AIED-like disease. The disease locus of the original AIED family maps to the same genetic interval as the CACNA1F gene, but efforts to reveal CACNA1F mutations in patients of the original AIED family have been unsuccessful. The specific aims of this study were to map the disease gene in a large Finnish family with X-linked cone-rod dystrophy and to identify the disease-causing genes in the patients of the Finnish cone-rod dystrophy family and the original AIED family. With the help of linkage and haplotype analyses, we could localize the disease gene of the Finnish cone-rod dystrophy family to the Xp11.4-Xq13.1 region, and thus establish a new genetic X-linked cone-rod dystrophy locus, CORDX3. Mutation analyses of candidate genes revealed three novel CACNA1F gene mutations: IVS28-1 GCGTC>TGG in CORDX3 patients, a 425 bp deletion, comprising exon 30 and flanking intronic regions in AIED patients, and IVS16+2T>C in an additional Finnish patient with a CSNB2-like phenotype. All three novel mutations altered splice sites of the CACNA1F gene, and resulted in defective pre-mRNA splicing suggesting altered or absent channel function as a disease mechanism. The analyses of CACNA1F mRNA also revealed novel alternative wt splice variants, which may enhance channel diversity or regulate the overall expression level of the channel. The results of our studies may be utilized in genetic counseling of the families, and they provide a basis for studies on the pathogenesis of these diseases. In the future, the knowledge of the genetic defects may be used in the identification of specific therapies for the patients.

Digital Photography in the Diagnosis and Follow-up of Ocular Diseases

Purpose: The aim of the present study was to develop and test new digital imaging equipment and methods for diagnosis and follow-up of ocular diseases. Methods: The whole material comprised 398 subjects (469 examined eyes), including 241 patients with melanocytic choroidal tumours, 56 patients with melanocytic iris tumours, 42 patients with diabetes, a 52-year old patient with chronic phase of VKH disease, a 30-year old patient with an old blunt eye injury, and 57 normal healthy subjects. Digital 50° (Topcon TRC 50 IA) and 45° (Canon CR6-45NM) fundus cameras, a new handheld digital colour videocamera for eye examinations (MediTell), a new subtraction method using the Topcon Image Net Program (Topcon corporation, Tokyo, Japan), a new method for digital IRT imaging of the iris we developed, and Zeiss photoslitlamp with a digital camera body were used for digital imaging. Results: Digital 50° red-free imaging had a sensitivity of 97.7% and two-field 45° and 50° colour imaging a sensitivity of 88.9-94%. The specificity of the digital 45°-50° imaging modalities was 98.9-100% versus the reference standard and ungradeable images that were 1.2-1.6%. By using the handheld digital colour video camera only, the optic disc and central fundus located inside 20° from the fovea could be recorded with a sensitivity of 6.9% for detection of at least mild NPDR when compared with the reference standard. Comparative use of digital colour, red-free, and red light imaging showed 85.7% sensitivity, 99% specificity, and 98.2 % exact agreement versus the reference standard in differentiation of small choroidal melanoma from pseudomelanoma. The new subtraction method showed growth in four of 94 melanocytic tumours (4.3%) during a mean ±SD follow-up of 23 ± 11 months. The new digital IRT imaging of the iris showed the sphincter muscle and radial contraction folds of Schwalbe in the pupillary zone and radial structural folds of Schwalbe and circular contraction furrows in the ciliary zone of the iris. The 52-year-old patient with a chronic phase of VKH disease showed extensive atrophy and occasional pigment clumps in the iris stroma, detachment of the ciliary body with severe ocular hypotony, and shallow retinal detachment of the posterior pole in both eyes. Infrared transillumination imaging and fluorescein angiographic findings of the iris showed that IR translucence (p=0.53), complete masking of fluorescence (p=0.69), presence of disorganized vessels (p=0.32), and fluorescein leakage (p=1.0) at the site of the lesion did not differentiate an iris nevus from a melanoma. Conclusions: Digital 50° red-free and two-field 50° or 45° colour imaging were suitable for DR screening, whereas the handheld digital video camera did not fulfill the needs of DR screening. Comparative use of digital colour, red-free and red light imaging was a suitable method in the differentiation of small choroidal melanoma from different pseudomelanomas. The subtraction method may reveal early growth of the melanocytic choroidal tumours. Digital IRT imaging may be used to study changes of the stroma and posterior surface of the iris in various diseases of the uvea. It contributed to the revealment of iris atrophy and serous detachment of the ciliary body with ocular hypotony together with the shallow retinal detachment of the posterior pole as new findings of the chronic phase of VKH disease. Infrared translucence and angiographic findings are useful in differential diagnosis of melanocytic iris tumours, but they cannot be used to determine if the lesion is benign or malignant.

Real Time Eye Tracking and Blink Detection with USB Cameras

A human-computer interface (HCI) system designed for use by people with severe disabilities is presented. People that are severely paralyzed or afflicted with diseases such as ALS (Lou Gehrig's disease) or multiple sclerosis are unable to move or control any parts of their bodies except for their eyes. The system presented here detects the user's eye blinks and analyzes the pattern and duration of the blinks, using them to provide input to the computer in the form of a mouse click. After the automatic initialization of the system occurs from the processing of the user's involuntary eye blinks in the first few seconds of use, the eye is tracked in real time using correlation with an online template. If the user's depth changes significantly or rapid head movement occurs, the system is automatically reinitialized. There are no lighting requirements nor offline templates needed for the proper functioning of the system. The system works with inexpensive USB cameras and runs at a frame rate of 30 frames per second. Extensive experiments were conducted to determine both the system's accuracy in classifying voluntary and involuntary blinks, as well as the system's fitness in varying environment conditions, such as alternative camera placements and different lighting conditions. These experiments on eight test subjects yielded an overall detection accuracy of 95.3%.