Features

Clinical findings from the EAOO – part 2

In another of his reports from Croatia, Bill Harvey describes some of the latest clinical findings that caught his attention at the recent European Academy Conference

As with any good conference, the materials presented embraced topics that ranged from those currently impacting on everyday practice, to those more research-based areas likely to influence practice in the future. The former was well represented by many of the key lectures. Dr Nicola Logan (Aston, UK) gave an excellent overview of the latest thinking concerning myopia and its management, something this publication has focused on over the past year. Similarly, the latest approach to dry eye disease as outlined in the recent TFOS DEWS 2 reports was explained by Dr Heiko Pult (Germany), while the impact upon eye care of the modern lifestyle in a digital age was covered well by Dr Daniella Nosch (Switzerland) and Elaine Grisdale (from ABDO).

For the latter, there were some excellent presentations based on either case studies or research findings. Here are a few that I found of interest.

Secondary glaucoma

Dr Brett Spence (USA) used three different case presentations to illustrate the challenges presented by secondary glaucomas. Case one involved a 62-year-old female patient of Northern European descent who presented with the following;

  • Intraocular pressures in the mid-30s mmHg
  • Bilateral optic neuropathy
  • Correlating visual field and optical coherence tomography loss
  • Nuclear sclerotic cataract
  • A family history of glaucoma

She also showed evidence of pseudoexfoliation. She was initially placed on topical glaucoma medications but did not reach the desired target pressure. She underwent combined cataract surgery with trabeculectomy. Her intraocular pressure improved and diagnostic test results then stabilised.

Case two was of a a 26-year-old keratoconus patient who had undergone corneal graft surgery. Due to constant moving around the US for his job, he delayed undergoing an eye examination. With six months between examinations and the use of topical fluorometholone ophthalmic suspension to prevent any graft rejection, he presented with a painless intraocular pressure of 47mmHg. Distinguishing clinical features at this presentation included an ipsilateral afferent pupillary defect, incipient posterior subcapsular cataract, and glaucomatous optic neuropathy. He was diagnosed with steroid-induced secondary glaucoma. He was subsequently placed on topical glaucoma medications, oral acetazolamide (a carbonic anhydrase inhibitor), and stopped from using the corticosteroid. He then was placed on what Dr Spense described as a ‘soft topical steroid, Lotemax, concurrent with glaucoma medications after several weeks. His pressures stabilised as did the adverse impact of the initial steroid.

The final case concerned a 37-year-old white male who presented with complaints of blurring in his right eye particularly when exercising. He had no other complaints other than moderate myopia for which he wore glasses. Examination showed an elevated intraocular pressure of 28mmHg in the right eye, and 22mmHg in the left. Transillumination iris defects were seen in the right eye along with a Krukenberg’s spindle (figure 1) and a prominent Zentmayer ring on the anterior capsule. He also showed a moderate myopic temporal tilt of the optic disc in the right eye. He was diagnosed with pigment dispersion syndrome of the right eye. The patient showed dense pigment covering the trabecular meshwork when assessed by video gonioscopy. Management included serial tonometry with a 5 to 8mmHg higher IOP monitored in the right eye, equivocal results from OCT measurement of the retinal nerve fibre layer and visual fields, and a decision was made to start treatment with an aqueous suppressant, such as a carbonic anhydrase inhibitor.

Figure 1: A Krukenberg spindle

In summing up, Dr Spense emphasised that secondary glaucomas may be more aggressive than primary open angle glaucoma and need to be managed accordingly.

Retinal anatomy

Doctors José González-Méijome and Ana Amorim-de-Sousa (University of Minho, Portugal) explained some of the complexities of the retina with a focus upon the photoreceptors. ‘The human retina is a complex tissue spread over an area of 1100mm2 where the light is transformed into an electrical sign and the visual information is firstly treated and modulated before it gets to the brain. There are three types of photoreceptors (described as L, M, or S), 11 different types of bipolar cells (Bc), three types of horizontal cells (Hc), 18 to 25 types of amacrine cells (Ac) and around 23 types of ganglion cell (Gc) in the mammalian retina, including the human species,’ they explained.

The centre of the fovea is composed mainly of L- and M-cones, with S-cones representing less than 12% of all cones and then decreasing towards periphery. L-and M- cones have their highest density at fovea (some 21000 and 40000 cells/degree, respectively), while for S-cones at the centre of fovea there are about 2500 cells/degree, reaching a maximum density of around 7500 S-cones/degree at approximately 3 degrees from the central fovea.

Three different types of horizontal cell have been described (HI, HII and HIII) and, despite their supposed connectivity function with photoreceptors (HI with cones and rods; HII only with cones; HIII L-M cones and alleged with rods), no information about the distribution of horizontal cells was found in the literature.

Eleven types of bipolar cell have been described:

  • One directly connected with rods (RB)
  • Seven concerned with information convergence from cones. Six of these are of a diffuse nature (DB) and one type of a giant bistratified nature (GBB)
  • Three are concerned with single-cones with contacts in a 1:1 relationship. These are called invaginating (iMBc), flat midget bipolar cells (fMBc) and the blue-cone bipolar cell (BB).

At the centre of the fovea there are only iMBc and fMBc connected with L- and M-cones (1iMBc and 1fMBc:1cone) out to 40 degrees eccentricity. The BB is connected to a single S-cone at the fovea but, as it moves away, starts to receive information from two to four S-cones with a maximum distribution at 3 degrees where they are found in a 70000 BB/degree concentration.

The six types of diffuse bipolar cells (DB) are similarly distributed along the retina with a density of around 2500 cells/mm2 (DB3 and DB6 at about 930 cells/mm2). The GBB is related with S-cones OFF-pathway and is usually connected to around 20 cones. Its distribution has a peak density of about 140000 per degree at 1 to 3 degrees’ eccentricity, decreasing to about 37500 per degree at 20 to 30 degrees’ eccentricity.

There is a lack of information with respect to the density and distribution of amacrine cells. However, it has been reported there is from 18 up to 25 different types of Ac within the retina.

There have been reported about 23 different types of ganglion cell (Gc). Like the bipolar cells, there are invaginating and flat midget/parvocellular types (iPGc and fPGc, respectively) responsible for red/green colour opponency and with a distribution of around 2800 cells/mm2 at 1mm of eccentricity, with a decreasing density up to 280 cells/mm2 at 15mm from the foveal area.

The S-cone Gc (blue/yellow) is a specialised cell that represents only 3% of all the retinal Gc with a spatial density distribution comparable to the S-cones, with approximately 400 cells/mm2 at the fovea and just 20 cells/mm2 in more peripheral areas.

Another well studied Gc is the so-called parasol Gc (MGc), also classified as invaginating (iMGc) and flat (fMGc), and this represents about 10% of the total Gc population, with only 2% of them at the fovea but increasing in density to the periphery to a peak density at 7mm from the nasal fovea with around 3400 cells/mm2 (based on studies on the macaque retina). These cells have responsibility for the detection of movement, depth perception and small changes in brightness. Some authors report no

significant differences in cell density between the four retinal quadrants (nasal, temporal, superior and inferior), while others observed significant differences along the horizontal and vertical meridians, reporting a higher cells density (up to about 1000 cells/mm2) in the nasal and superior peripheral retina.

A somewhat mind-blowing complexity but worth being made aware of the latest thinking in retina microstructure.

Dark adaptation

Dark adaptation is a standard methodology for assessing rod function, explained Dr Jasleen Jolly of Oxford Eye Hospital. The test is undergoing a resurgence as there are an increasing number of clinical trials for the treatment of rod-cone dystrophies. Dark adaptometry is a long process and can be a burden on patients. The FST test (Diagnosys LLC, Cambridge, UK) and the Maculogix (figure 2) have been developed as alternatives to the lab technique of the Goldman Weekers dark adaptometer for the characterisation of dark adaptation. Scotopic microperimetry techniques are also being developed.

Jolly’s team studied a group of patients with choroideraemia who underwent scotopic testing with both full field dark adaptometry and FST using the Espion 2/3. A subset of patients underwent localised measurements 5 degrees superior to the fovea using the Maculogix. Three distinct patterns of dark adaptation curves were identified. FST was significantly different between these groups (P < 0.001). The FST was well correlated with the final threshold (r = 0.94, P < 0.001). The Espion dark adaptation threshold at 18 minutes was well correlated with the final threshold (r = 0.81, P < 0.001). However, the Maculogix results did not correlate well with either slope (P = 0.27).

The team concluded that the FST is a viable alternative to plotting full dark adaptation curves. The threshold at 18 minutes appears to be related to the final threshold, although it cannot predict it. This indicates that the full adaptation time may not be necessary for the assessment of rod function. The Maculogix conducts measurements over 18 minutes. It may be a viable alternative to the Espion for clinical trials. However, more information is required about the scaling of the dB scale used by the equipment in order to directly compare the methodologies. The Maculogix measurement location did not encompass viable retina in three patients so more work is needed around the variability across the retina to allow flexibility with testing regimes. The Maculogix is already in use in many optometry clinics in the US.