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1.  Angle closure in younger patients. 
PURPOSE: Angle-closure glaucoma is rare in children and young adults. Only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients in our database aged 40 or younger with angle closure. METHODS: Our database was searched for patients with angle closure who were 40 years old or younger. Data recorded included age at initial consultation; age at the time of diagnosis; gender; results of slit-lamp examination, gonioscopy, and ultrasound biomicroscopy (from 1993 onward); clinical diagnosis; and therapy. Patients with previous incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. RESULTS: Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age (+/- SD) at the time of consultation was 34.4 +/- 9.4 years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients), iridociliary cysts (8 patients), retinopathy of prematurity (7 patients), uveitis (5 patients), isolated nanophthalmos (3 patients), relative pupillary block (2 patients), Weill-Marchesani syndrome (3 patients), and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. CONCLUSION: The etiology of angle closure in young persons is different from that in the older population and is typically associated with structural or developmental ocular anomalies rather than relative pupillary block. Following laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention.
PMCID: PMC1358963  PMID: 12545694
2.  Compound heterozygosity for a novel and a recurrent MFRP gene mutation in a family with the nanophthalmos-retinitis pigmentosa complex 
Molecular Vision  2009;15:1794-1798.
Purpose
To report a new familial case of the recently described autosomal recessive syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen, which arises from compound heterozygosity for Membrane Frizzled-Related Protein (MFRP) mutations in a sibling pair of Mexican origin.
Methods
Ophthalmological assessment included slit-lamp and dilated fundus examination, applanation tonometry, fundus photography, A-mode and B-mode ultrasound examination, electroretinogram, fluorescein retinal angiography, optical coherence tomography, and electrooculogram in both affected siblings. Molecular genetic analysis consisted of PCR amplification and direct automated sequence of the complete coding region of the MFRP gene. In addition, allele-specific cloning and sequencing techniques were used to characterize a heterozygous MFRP frameshift mutation.
Results
Clinical examination revealed high hyperopia of > +16 diopters while electroretinographic and fluorangiographic studies demonstrated a retinal dystrophy compatible with retinitis pigmentosa. Ultrasound examination showed nanophthalmos (eye axial length <15 mm) and optic disc drusen while optical coherence tomography evidenced cystoid macular edema. Nucleotide sequencing in DNA from both affected siblings disclosed the presence of two MFRP mutations: a novel heterozygous point mutation predicting a nonsense change from tyrosine (TAC) to a stop signal (TAA) at codon 317, and a heterozygous 1 bp deletion in exon 5, predicting a prematurely truncated protein (p.Asn167ThrfsX25).
Discussion
The third known family with the syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen is presented. This is the first demonstration of compound heterozygosity for MFRP mutations as the source of the disease. The affected siblings described here are the youngest patients with the disease reported to date and the comparison of their clinical data with previous individuals with this syndrome suggest that some aspects of the phenotype are probably age-dependent.
PMCID: PMC2742641  PMID: 19753314
3.  Bilateral nanophthalmos, pigmentary retinal dystrophy, and angle closure glaucoma--a new syndrome? 
An unusual case of bilateral nanophthalmos with pigmentary retinal dystrophy and angle closure glaucoma is presented. This is probably the first published report of the established association of all these three entities in the same patient. The aetiological possibilities and clinical significance are discussed.
Images
PMCID: PMC1040691  PMID: 4016062
4.  The management of glaucoma in nanophthalmos. 
Patients with nanophthalmos are prone to develop a chronic painless type of glaucoma in middle age, probably due to the natural increase in the size of the lens which is already relatively too large for the small eye. Although the underlying mechanism is obscure, a slowly progressive "creeping" chronic angle-closure is postulated, but gonioscopic evaluation is difficult due to the shallow anterior chamber, with grade I and slit angles. Response to medical treatment is poor and miotics may even make the condition worse by producing relative pupillary block and by relaxing the lens zonule. Ordinary glaucoma surgery is to be avoided in nanophthalmos because of the fear of postoperative ciliary-block malignant glaucoma. Periopheral iridectomy performed in five eyes at an advanced stage of the chronic angle-closure did not facilitate glaucoma control in three eyes, and in two eyes in which the operation was combined with posterior sclerotomy, the eyes became blind from vitreous hemorrhage. Lenx extraction in five eyes controlled the glaucoma but was followed by choroidal effusion and nonrhegmatogenous retinal detachements in two eyes and blindness in another eye when combined with a posterior sclerotomy. No firm therapeutic recommendations can be made on the basis of the author's experience in the six reported cases. Conventional medical therapy seems ineffectual even when begun early in the glaucoma. Conventional glaucoma surgery must be performed early, before permanent damage to the outflow mechanism occurs but removal of the lens must be anticipated. The surgeon must also remain aware of the high incidence of serious posterior-segment complications which inexplicably follow glaucoma or lens surgery in nanophthalmos, as described by Brockhurst.
Images
PMCID: PMC1311447  PMID: 1246819
5.  Optic disc morphology in pigmentary glaucoma 
AIM—To evaluate the morphology of the optic nerve head in eyes with pigmentary glaucoma.
METHODS—Colour stereo optic disc photographs of 62 patients with pigmentary glaucoma and 566 patients with primary open angle glaucoma were morphometrically evaluated. By prestudy selection, mean visual field defect and neuroretinal rim area were not significantly different between the two groups (p=0.89 and p=0.45).
RESULTS—The pigmentary glaucoma group did not vary significantly (p >0.10) from the primary open angle glaucoma group in size and shape of the optic disc, configuration of neuroretinal rim, depth of optic cup, area of alpha zone of parapapillary atrophy, diameter of retinal vessels at the disc border, and frequency of disc haemorrhages and localised retinal nerve fibre layer defects. The beta zone of parapapillary atrophy was slightly, but not statistically significantly (p=0.06), smaller in the pigmentary glaucoma group. The mean maximal intraocular pressure and mean intraocular pressure amplitude were significantly (p<0.001) higher in the pigmentary glaucoma group.
CONCLUSIONS—In contrast with the characteristic morphology of the anterior segment and despite significantly higher intraocular pressure peaks and a larger pressure amplitude, eyes with pigmentary glaucoma compared with eyes with primary open angle glaucoma do not show a pathognomonic morphology of the optic disc and retinal nerve fibre layer. The slightly smaller beta zone of parapapillary atrophy may correspond to higher intraocular pressure in pigmentary glaucoma.

 Keywords: optic disc morphology; pigmentary glaucoma; secondary open angle glaucoma
PMCID: PMC1722721  PMID: 9828769
6.  Prevalence of glaucoma in Thailand: a population based survey in Rom Klao District, Bangkok 
The British Journal of Ophthalmology  2003;87(9):1069-1074.
Aim: To determine prevalence, demography, mechanism, and visual morbidity of glaucoma in urban Thai people.
Methods: 790 subjects aged 50 years or older from Rom Klao district, Bangkok, Thailand, were enumerated in a population based cross sectional study. Each subject underwent the following investigations: visual acuity, visual field testing, slit lamp examination, applanation tonometry, gonioscopy, and an optic disc examination after mydriasis. Main outcome measures included visual acuity (logMAR), visual fields, intraocular pressure (IOP), gonioscopic characteristics, vertical cup/disc ratio (VCDR), prevalence of types of glaucoma. Glaucoma was diagnosed on the basis of optic disc appearance and visual field defects. In eyes in which the optic disc could not be examined, glaucoma was diagnosed when visual acuity was <3/60 and either IOP >99.5th percentile or there was evidence of previous glaucoma surgery.
Results: 701 subjects were examined (response rate 88.7%). In eyes with “normal” suprathreshold visual fields, the mean IOP was 13.3 mm Hg (97.5th percentile = 20 mm Hg). The 97.5th and 99.5th percentiles of VCDR were 0.72 and 0.86 respectively. Of the 701 subjects examined in the clinic, 27 had glaucoma (3.8%, 95% CI: 2.5 to 5.6), 16 had primary open angle glaucoma (POAG, prevalence 2.3%, 95% CI: 1.3 to 3.7), six were primary angle closure glaucoma (PACG, prevalence 0.9%, 95% CI: 0.3 to 1.9), and five were secondary glaucoma (SecG, prevalence 0.7%, 95% CI: 0.2 to 1.7). Among the 43 unilaterally blind subjects, glaucoma was the cause in five subjects (12%). One subject was bilaterally blind due to glaucoma (prevalence 11%, 95% CI: 0.3 to 61.9). 28 people (4%) were glaucoma suspects on the basis of optic disc appearance and six on the basis of visual fields only. 98 subjects (14%) had “occludable angles” in either eye, 22 of whom had primary angle closure (PAC, prevalence 3.1%, 95% CI: 1.9 to 4.7); 14 had peripheral anterior synechiae in either eye and eight had ocular hypertension (OHT).
Conclusions: POAG accounted for 67% of all glaucoma, PACG 21%, and secondary glaucomas 12%. Glaucoma was the second most common cause of severe unilateral visual loss.
PMCID: PMC1771843  PMID: 12928267
glaucoma; Thailand
7.  A novel crumbs homolog 1 mutation in a family with retinitis pigmentosa, nanophthalmos, and optic disc drusen 
Molecular Vision  2012;18:2447-2453.
Purpose
The purpose of this study is to identify the genetic defect in a Turkish family with autosomal recessive retinitis pigmentosa, nanophthalmos, and optic disc drusen.
Methods
Ophthalmological examinations consisted of measuring the best-corrected visual acuity and the refractive error, electroretinography, optical coherence tomography, B-mode ultrasonography, and fundus photography. The involvement of the membrane frizzled-related protein (MFRP) gene in this family was studied with direct DNA sequencing of the coding exons of MFRP and with linkage analysis with microsatellite markers. After MFRP was excluded, genome-wide homozygosity mapping was performed with 250 K single nucleotide polymorphism (SNP) microarrays. Mutation analysis of the crumbs homolog 1 (CRB1) gene was performed with direct sequencing.
Results
Ophthalmological evaluation of both affected individuals in the family revealed a decreased axial length (18–19 mm), retinal dystrophy, macular edema, and hyperopia of >+8.0 diopters. Sequencing of MFRP did not reveal any pathogenic changes, and microsatellite marker analysis showed that the chromosomal region did not segregate within the disease in this family. Genome-wide homozygosity mapping using single nucleotide polymorphism microarrays revealed a 28-Mb homozygous region encompassing the CRB1 gene, and direct sequencing disclosed a novel homozygous missense mutation (p.Gly833Asp) in CRB1.
Conclusions
Previous studies associated mutations in the MFRP gene with the syndrome nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen. In this study, we demonstrated that a similar disease complex can be caused by mutations in the CRB1 gene.
PMCID: PMC3472923  PMID: 23077403
8.  Acute Angle-Closure Glaucoma from Spontaneous Massive Hemorrhagic Retinal Detachment 
Purpose
To report a case of acute angle-closure glaucoma resulting from spontaneous hemorrhagic retinal detachment.
Methods
An 81-year-old woman visited our emergency room for severe ocular pain and vision loss in her left eye. Her intraocular pressures (IOPs) were 14 mmHg in the right eye and 58 mmHg in the left eye. Her visual acuity was 0.4 in the right eye but she had no light perception in the left eye. The left anterior chamber depth was shallow and gonioscopy of the left eye showed a closed angle. In comparison, the right anterior chamber depth was normal and showed a wide, open angle. Computed tomography and ultrasonography demonstrated retinal detachment due to subretinal hemorrhage. After systemic and topical antiglaucoma medications failed to relieve her intractable severe ocular pain, she underwent enucleation.
Results
The ocular pathology specimen showed that a large subretinal hemorrhage caused retinal detachment and pushed displaced the lens-iris diaphragm, resulting in secondary angle-closure glaucoma.
Conclusions
Prolonged anticoagulant therapy may cause hemorrhagic retinal detachment and secondary angle-closure glaucoma. If medical therapy fails to relieve pain or if there is suspicion of an intraocular tumor, enucleation should be considered as a therapeutic option.
doi:10.3341/kjo.2007.21.1.61
PMCID: PMC2629687  PMID: 17460436
Acute angle-closure glaucoma; Hemorrhage; Retinal detachment
9.  Molecular analysis of CHX10 and MFRP in Chinese subjects with primary angle closure glaucoma and short axial length eyes 
Molecular Vision  2008;14:1313-1318.
Purpose
The genetic basis of primary angle closure glaucoma (PACG) has yet to be elucidated. Ocular characteristics related to PACG such as short hyperopic eyes with shallow anterior chambers suggest the involvement of genes that regulate ocular size. CHX10, a retinal homeobox gene associated with microphthalmia, and MFRP, the membrane-type frizzled-related protein gene underlying recessive nanophthalmos, represent good candidate genes for PACG due to the association with small eyes. To investigate the possible involvement of CHX10 and MFRP in PACG, we sequenced both genes in PACG patients with small ocular dimensions.
Methods
One hundred and eight Chinese patients with axial lengths measuring 22.50 mm or less were selected for analysis. Ninety-three age- and ethnically-matched control subjects were also screened. Genomic DNA was extracted from leukocytes of peripheral blood samples, and the exons of CHX10 and MFRP were amplified by polymerase chain reaction (PCR) and subjected to bidirectional sequencing and analysis.
Results
All study patients were Chinese with a mean age of 66.2±9.1 years (range 46–86). There were 77 females (71.3%). Forty-nine out of the one hundred and eight subjects had previous symptomatic PACG, and 59 had asymptomatic PACG. The mean axial length was 21.90±0.50 mm (range 19.98–22.50 mm). We identified a possible disease-causing variant in CHX10 (c.728G>A) resulting in Gly243Asp substitution in one patient. This variant was not found in 215 normal controls. Several CHX10 and MFRP polymorphisms were also identified.
Conclusions
Our results do not support a significant role for CHX10 or MFRP mutations in PACG.
PMCID: PMC2480479  PMID: 18648522
10.  Ocular biometry in occludable angles and angle closure glaucoma: a population based survey 
Aim: To compare ocular biometric values in a population based sample of eyes with occludable angles, angle closure glaucoma, and normal subjects.
Method: 2850 subjects from a population based glaucoma prevalence study underwent complete ocular examination including indentation gonioscopy. Ocular biometry was performed in all subjects classified to have occludable angles (n = 143); angle closure glaucoma (n = 22), and a random subgroup of 419 normal subjects. Ocular biometry readings between the groups were compared and statistically analysed using “t,” “z,” and Mann-Whitney U tests.
Results: The mean age among subjects with occludable angles (54.43 (SD 9.53) years) and angle closure glaucoma (57.45 (8.5) years) was significantly higher (p<0.001) than normal subjects (49.95 (9.95) years). Axial length was shorter (p<0.001) in the occludable angle group (22.07 (0.69) mm) compared to the normal group (22.76 (0.78) mm). Anterior chamber depth (ACD) was shallower (p<0.001) among subjects with occludable angles (2.53 (0.26) mm) than normal subjects (3.00 (0.30) mm). Lens thickness (LT) was greater (p<0.001) in people with occludable angles (4.40 (0.53) mm) compared to normal subjects (4.31 (0.31) mm). No significant difference was noted in axial length, ACD (p = 0.451), and LT (p = 0.302) between angle closure glaucoma and occludable eyes.
Conclusion: South Indian eyes with angle closure glaucoma and occludable angles seem to have significantly shorter axial lengths, shallower anterior chambers and greater lens thickness compared to the normal group.
PMCID: PMC1771625  PMID: 12642298
11.  Ophthalmic Manifestations and Histopathology of Infantile Nephropathic Cystinosis: Report of a Case and Review of the Literature 
Survey of ophthalmology  2007;52(1):97-105.
Cystinosis is a rare autosomal recessive metabolic disorder characterized by the intracellular accumulation of cystine, the disulfide of the amino acid cysteine, in many organs and tissues. Infantile nephropathic cystinosis is the most severe phenotype. Corneal crystal accumulation and pigmentary retinopathy were originally the most commonly described ophthalmic manifestations, but successful kidney transplantation significantly changed the natural history of the disease. As cystinosis patients now live longer, long-term complications in extrarenal tissues including the eye, have become apparent. A case of an adult patient with infantile nephropathic cystinosis is reported. He presented with many long-term ocular complications of cystinosis. After 4 years of follow-up, the patient died from sepsis. Pathology of the phthisical eyes demonstrated numerous electron transparent polygonal spaces, bounded by single membrane, in corneal cells, retinal pigment epithelial cells, and even choroidal endothelial cells. The ophthalmic manifestations and pathology of infantile nephropathic cystinosis are discussed and reviewed in light of the current report and other cases in the literature.
doi:10.1016/j.survophthal.2006.10.006
PMCID: PMC1850966  PMID: 17212992
cystine; cystinosis; eye; histopathology; infantile nephropathic cystinosis; lysosome
12.  Gonioscopic Features in Patients with Acute and Chronic Angle-Closure Glaucoma 
Background: A number of ocular biometric parameters, iris hiotologic and anatomic characters have been suggested as inciting factors for converting patients with narrow angle to angle-closure glaucoma. This study was conducted to determine if there was any goniscopic difference between patients with acute angle-closure glaucoma (AACG) and chronic angle-closure glaucoma (CACG).
Methods: The study is a retrospective analysis of the charts of 97 patients with asymmetric CACG and 15 patients with unilateral AACG. The age, sex, type of glaucoma, gonioscopic findings and optic nerve head cup/disc ratio were recorded for all patients. Dynamic gonioscopy and Spaeth’s convention were used to grade the drainage angle. The eyes with AACG or more optic nerve damage in CACG groups were considered as involved eye, and the contralateral eyes in the AACG and CACG groups were considered as noninvolved and less-involved, respectively.
Results: There was no significant difference between patients with AACG and CACG in terms of age, gender, refraction, and laterality of the involved eyes. In intragroup analysis, no significant difference was observed for distribution of iris attachment, irido-corneal angle, iris configuration, or trabecular pigmentation. In intergroup analysis, the superior iris was attached more anterior in the involved eyes of AACG compared to that in CACG (P=0.007). Moreover, the iris root attachment was also more anterior in both the superior (P=0.001) and inferior (P=0.002) angles of the noninvolved eyes of AACG vs. than those in the less-involved eyes of CACG group.
Conclusion: The findings of the study indicate that there is no significant difference between the eyes with AACG or CACG in terms of goniscopic findings. However, the superior iris attachment was located more anterior in eyes with AACG compared to that in eyes with CACG.
PMCID: PMC3559115  PMID: 23365471
Angle-closure glaucoma; gonioscopy; iris
13.  Prevalence and distribution of glaucoma in central India (Glaucoma Survey - 2001) 
Purpose:
A community-based survey was conducted in Rajnandangaon district of Chhattisgarh state of central India in 2001 to assess the prevalence of glaucoma in the age group of ≥35 years.
Design:
Community-based cross-sectional survey
Materials and Methods:
Ophthalmologists measured ocular pressure using Perkins applanation tonometer. Best corrected visual acuity was checked by ETDRS chart. After dilating the pupil the fundus was examined. A sketch diagram was drawn to note glaucomatous changes in optic disc and the surrounding retina. The field of vision was tested on Bjerrum screen. Gonioscopy was performed to determine type of glaucoma. Persons and their relatives were interviewed to find out risk factors and glaucoma treatment in the past.
Results:
Seven thousand four hundred and thirty-eight (87.3%) persons were examined. The age-sex standardized prevalence of glaucoma was 3.68% (95% CI 3.27 to 4.07). Gender variation of glaucoma was not significant. [OR = 1.13 (CI 95% 0.88 to 1.44)] Glaucoma varied significantly by age groups. (Χ2 = 48.2, degree of freedom = 3 P <0.001) Among those patients diagnosed to suffer from glaucoma, the proportion of open angle, closed angle, secondary glaucoma, ocular hypertension and glaucoma suspects was 13.1%, 21.2%, 21.2%, 14.5% and 30% respectively. Different types of visual disabilities were associated with glaucoma. However, unilateral blindness in glaucoma was unusual. Twenty-five per cent of the glaucoma cases were detected for the first time during the survey.
Conclusions:
The prevalence of glaucoma was high and the angle closure type was more compared to the open angle glaucoma.
PMCID: PMC2636061  PMID: 18158405
Blindness; glaucoma; India; low vision; prevalence study
14.  Clinicopathological review of 1146 enucleations (1980-90). 
The clinicopathological data of 1146 enucleated eyes obtained from 1146 patients (485 females and 661 males; mean age 57.4 (SD 21.6) years) between 1980 and 1990 were reviewed. The most common underlying diseases included trauma (37.4%), malignant tumours (19.6%), systemic diseases (diabetes, vascular diseases) (17.1%), surgical diseases (retinal detachment, glaucoma, cataract, corneal dystrophy) (14.1%), infection and inflammation (7%). The most frequent indications for enucleation were secondary angle closure glaucoma (34.9%), ocular malignant tumours (21.7%), atrophia or phthisis bulbi (18.7%), ocular infectious or inflammatory disease (14.7%), and recent trauma (enucleation was performed within the first month after trauma) (11.2%). Histopathologically, diagnoses included secondary angle closure (691 eyes or 60.3%), rubeosis iridis (550 or 48%), endothelialisation of the iridocorneal angle (198 or 17.3%), and retrocorneal membrane (143 or 12.5%). These data indicate that rubeosis iridis, often followed by irreversible secondary angle closure, represents the most common pathogenetic reason for enucleating eyes. Management procedures must be directed towards the prevention or consequent therapy of rubeosis iridis.
PMCID: PMC504758  PMID: 8199109
15.  Acquired retinoschisis resolved after 23Gage pars plana vitrectomy in posterior microphthalmos 
BMC Ophthalmology  2014;14:65.
Background
Posterior microphthalmos combined with acquired retinoschisis is a rare entity. This report presents a case of acquired retinoschisis in a patient with posterior microphthalmos and discusses the management for such disease. The patient exhibited acquired peripheral retinal schisis in both eyes.
Case presentation
The patient presented with a fix scotoma and decrease in visual acuity for 2 weeks in his left eye. Ocular examination revealed that his best-corrected visual acuity was 0.6 in right eye and 0.2 in left eye. The patient had amblyopia because of hyperopia with spherical equivalent of +11.75 diopters in the right eye and +12.00 diopters in the left eye. The axial lengths were 18.41 mm in right and 18.43 mm in left eyes respectively. Slip lamp examination found normal anterior segments. Funduscopy showed bilateral retinoschisis in inferotemporal retina. The schisis in right eye was limited to peripheral retina whereas the schisis in left eye was bullous type. The schisis in the left eye extended from the periphery to the posterior macular region in left eye. A pars plana vitrectomy was performed in the left eye and visual acuity was restored to 0.6.
Conclusion
Posterior microphthalmos combined with retinoschisis is rare. When it appears in peripheral retina, the schisis remains stable. In cases where the schisis extends to posterior pole and affects the macula, surgery in the form of pars plana vitrectomy could be an option.
doi:10.1186/1471-2415-14-65
PMCID: PMC4045141  PMID: 24884506
Microphthalmos; Acquired retinoschisis; Pars plana vitrectomy
16.  Diurnal Tension Curves for Assessing the Development or Progression of Glaucoma 
Executive Summary
Clinical Need: Condition and Target Population
There are two main types of glaucoma, primary open angle (POAG) and angle closure glaucoma, of which POAG is the more common type. POAG is diagnosed by assessing degenerative changes in the optic disc and loss of visual field (VF). Risk factors for glaucoma include an increase in intraocular pressure (IOP), a family history of glaucoma, older age and being of African descent. The prevalence of POAG ranges from 1.1% to 3.0% in Western populations and from 4.2% to 8.8% in populations of African descent.
Usually the IOP associated with POAG is elevated above the normal distribution (10-20 mmHg), but when IOP is not elevated it is often referred to as normal-tension glaucoma (NTG). In population based studies, approximately one-third to half of the patients with glaucomatous VF loss have normal IOP on initial examination.
People with elevated IOP (>21 mmHg), but with no evidence of optic disc or VF damage have ocular hypertension. It has been estimated that 3 to 6 million people in the United States including 4% to 7% of those older than 40 years have elevated IOP without detectable glaucomatous damage on standard clinical tests. An Italian study found the overall prevalence of ocular hypertension, POAG, and NTG in 4,297 people over 40 years of age to be 2.1%, 1.4% and 0.6% respectively.
Diurnal Curves for Intraocular Pressure Measurement
Diurnal Curve
In normal individuals, IOP fluctuates 2 to 6 mmHg over a 24 hour period. IOP is influenced by body position with higher readings found in the supine relative to the upright position. As most individuals sleep in the supine position and are upright during the day, IOP is higher on average in people, both with and without glaucoma, in the nocturnal period. IOP is generally higher in the morning compared to the afternoon.
Multiple IOP measurements over the course of a day can be used to generate a diurnal curve and may have clinical importance in terms of diagnosis and management of patients with IOP related conditions since a solitary reading in the office may not reveal the peak IOP and fluctuation that a patient experiences. Furthermore, because of diurnal and nocturnal variation in IOP, 24-hour monitoring may reveal higher peaks and wider fluctuations than those found during office-hours and may better determine risk of glaucoma progression than single or office-hour diurnal curve measurements.
There is discrepancy in the literature regarding which parameter of IOP measurement (e.g., mean IOP or fluctuation/range of IOP) is most important as an independent risk factor for progression or development of glaucoma. The potential for increased rates or likelihood of worsening glaucoma among those with larger IOP swings within defined time periods has received increasing attention in the literature.
According to an expert consultant:
The role of a diurnal tension curves is to assess IOP in relationship to either a risk factor for the development or progression of glaucoma or achievement of a target pressure which may direct a therapeutic change.
Candidates for a diurnal curve are usually limited to glaucoma suspects (based on optic disc changes or less commonly visual field changes) to assess the risk for development of glaucoma or in patients with progressive glaucoma despite normal single office IOP measurements.
Clinically diurnal tension curves are used to determine the peak IOP and range.
Single IOP Measurements
Intraocular pressure fluctuation as a risk factor for progression of glaucoma has also been examined without the use of diurnal curves. In these cases, single IOP measurements were made every 3-6 months over several months/years. The standard deviation (SD) of the mean IOP was used as a surrogate for fluctuation since no diurnal tension curves were obtained.
Objective
To determine whether the use of a diurnal tension curve (multiple IOP measurements over a minimum 8 hour duration) is more effective than not using a diurnal tension curve (single IOP measurements) to assess IOP fluctuation as a risk factor for the development or progression of glaucoma.
To determine whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma despite normal single office IOP measurements and leads to a more effective disease management strategy.
Research Methods
Literature Search
Search Strategy
A literature search was performed on July 22, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2006 until July 14, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
Open angle glaucoma (established or OHT high risk) in an adult population
IOP measurement by Goldmann applanation tonometry (the gold standard)
Number and timing of IOP measurements explicitly reported (e.g., 5 measurements a day for 5 visits to generate a diurnal curve or 1 measurement a day [no diurnal curve] every 3 months for 2 years)
IOP parameters include fluctuation (range [peak minus trough] or standard deviation) and mean
Outcome measure = progression or development of glaucoma
Study reports results for ≥ 20 eyes
Most recent publication if there are multiple publications based on the same study
Exclusion Criteria
Angle closure glaucoma or pediatric glaucoma
Case reports
IOP measured by a technique other than GAT (the gold standard)
Number and timing of IOP measurements not explicitly reported
Outcomes of Interest
Progression or development of glaucoma
Conclusion
There is very low quality evidence (retrospective studies, patients on different treatments) for the use of a diurnal tension curve or single measurements to assess short or long-term IOP fluctuation or mean as a risk factor for the development or progression of glaucoma.
There is very low quality evidence (expert opinion) whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma, despite normal single office IOP measurements, and leads to a more effective disease management strategy.
PMCID: PMC3377558  PMID: 23074414
17.  Changing Trends of Imaging in Angle Closure Evaluation 
ISRN Ophthalmology  2012;2012:597124.
Primary angle closure glaucoma (PACG) is a significant cause of visual disability worldwide. It predominantly affects the Eastern and South Asian population of the world. Early detection of anatomically narrow angles is important, and the subsequent prevention of visual loss from PACG depends on an accurate assessment of the anterior chamber angle (ACA). Gonioscopy has given way to modern day imaging technologies such as ultrasound biomicroscopy (UBM) and more recently, anterior segment optical coherence tomography (AS-OCT). Ultrasound biomicroscopy provides objective, high-resolution images of anterior segment anatomy, including the cornea, iris, anterior chamber, anterior chamber angle, and ciliary body. Optical coherence tomography (OCT) is a noncontact optical signal acquisition and processing device that provides magnified, high-resolution cross-sectional images of ocular tissues. Recent technological advances towards three-dimensional visualization broadened the scope of AS-OCT in ophthalmologic evaluation. Optical coherence tomography systems use low-coherence, near-infrared light to provide detailed images of anterior segment structures at resolutions exceeding that of UBM. This paper summarizes the clinical application of UBM and OCT for assessment of anterior segment in glaucoma.
doi:10.5402/2012/597124
PMCID: PMC3914273  PMID: 24558589
18.  Prospective case series on trabecular-iris angle status after an acute episode of phacomorphic angle closure 
AIM
To investigate the trabecular-iris angle with ultrasound biomicroscopy (UBM) post cataract extraction after an acute attack of phacomorphic angle closure.
METHODS
This prospective study involved 10 cases of phacomorphic angle closure that underwent cataract extraction and intraocular lens insertion after intraocular pressure (IOP) lowering. Apart from visual acuity and IOP, the trabecular-iris angle was measured by gonioscopy and UBM at 3 months post attack.
RESULTS
In 10 consecutive cases of acute phacomorphic angle closure from December 2009 to December 2010, gonioscopic findings showed peripheral anterior synechiae (PAS) ≤ 90° in 30% of phacomorphic patients and a mean Shaffer grading of (3.1±1.0). UBM showed a mean angle of (37.1°±4.5°) in the phacomorphic eye with the temporal quadrant being the most opened and (37.1°±8.0°) in the contralateral uninvolved eye. The mean time from consultation to cataract extraction was (1.4±0.7) days and the mean total duration of phacomorphic angle closure was (3.6±2.8) days but there was no correlation to the degree of angle closure on UBM (Spearman correlation P=0.7). The presenting mean IOP was (50.5±7.4) mmHg and the mean IOP at 3 months was (10.5±3.4) mmHg but there were no correlations with the degree of angle closure (Spearman correlations P=0.9).
CONCLUSION
An open trabecular-iris angle and normal IOP can be achieved after an acute attack of phacomorphic angle closure if cataract extraction is performed within 1 day - 2 days after IOP control. Gonioscopic findings were in agreement with UBM, which provided a more specific and object angle measurement. The superior angle is relatively more narrowed compared to the other quadrants. All contralateral eyes in this series had open angles.
doi:10.3980/J.ISSN.2222-3959.2013.01.14
PMCID: PMC3580253  PMID: 23549291
angle; ultrasound biomicroscopy; phacomorphic; intraocular pressure
19.  The association of membrane frizzled-related protein (MFRP) gene with acute angle-closure glaucoma – a pilot study 
Molecular Vision  2008;14:1673-1679.
Purpose
The membrane frizzled-related protein (MFRP) has been proposed as a probable candidate gene for extreme hyperopia and nanophthalmos, which are factors for angle-closure glaucoma. The purpose of our study was to investigate whether there are significant associations between angle-closure glaucoma and sequence variants in the MFRP gene reported previously in Taiwanese subjects.
Methods
Genomic DNA was collected from 63 subjects with angle-closure glaucoma and 66 age-matched and gender-matched controls without angle-closure glaucoma. Three sequence variants were detected by polymerase chain reaction (PCR) and direct sequencing in all of the cases and controls.
Results
None of the three sequence variants showed a significant result in terms of association with disease. The pairwise linkage disequilibrium (LD) mapping confirmed that these alleles have a comparatively strong LD index greater than 0.7 for D' and greater than 0.4 for r2 at these polymorphisms. However, we found there were no statistical associations between any of the three sequence variants located on MFRP and angle-closure glaucoma.
Conclusions
In our pilot study, variations that we tested in MFRP were not associated with the development of acute angle-closure glaucoma in Taiwanese subjects.
PMCID: PMC2532703  PMID: 18781223
20.  Progressive hemifacial atrophy. A natural history study. 
PURPOSE: To describe two very different natural history courses in 2 patients with hemifacial atrophy. Progressive hemifacial atrophy (Parry-Romberg syndrome, Romberg syndrome, PHA) is characterized by slowly progressive atrophy, frequently involving only one side of the face, primarily affecting the subcutaneous tissue and fat. The onset usually occurs during the first 2 decades of life. The cause and pathophysiology are unknown. Ophthalmic involvement is common, with progressive enophthalmos a frequent finding. Pupillary disturbances, heterochromia, uveitis, pigmentary disturbances of the ocular fundus, and restrictive strabismus have also been reported. Neurologic findings may be present, but the natural history and progression of ocular findings are often not described in the literature. METHODS: We studied the records and present findings of 2 patients with progressive hemifacial atrophy who were observed in our institution over a 10-year period. RESULTS: Both patients showed progression of ophthalmic findings, primarily on the affected side. One patient has had chronic uveitis with secondary cataract and glaucoma, in addition to retinal pigmentary changes. She also had a third-nerve paresis of the contralateral eye and mild seizure activity. The other patient had mild uveitis, some progression of unilateral retinal pigmentary changes, and a significant increase in hyperopia in the affected eye, in addition to hypotony at age 19 without a clear cause, but with secondary retinal and refractive changes. CONCLUSION: Ocular manifestations of progressive hemifacial atrophy are varied, but can progress from mild visual impairment to blindness.
Images
PMCID: PMC1312058  PMID: 8719679
21.  The Role of Anterior Segment Optical Coherence Tomography in Glaucoma 
Journal of Ophthalmology  2012;2012:476801.
The anterior segment optical coherence tomography provides an objective method to assess the anterior segment of the eye, including the anatomy of the anterior chamber angle. This technology allows both qualitative and quantitative analyses of the angle and has shown potential in detecting and managing angle-closure glaucoma. In addition, it has a role in identifying pathology in some forms of secondary open-angle glaucoma and postsurgical management of glaucoma. Limitations of this technology include its cost and inability to visualize well structures posterior to the iris, such as the ciliary body. This paper focuses on potential benefits and limitations of anterior segment optical coherence tomography when compared with conventional gonioscopy and ultrasound biomicroscopy. Various clinical entities will be described to discuss its potential role in glaucoma practice.
doi:10.1155/2012/476801
PMCID: PMC3415232  PMID: 22900146
22.  Central corneal thickness determined with optical coherence tomography in various types of glaucoma 
The British Journal of Ophthalmology  2000;84(11):1233-1237.
AIMS—To evaluate central corneal thickness determined by optical coherence tomography (OCT) in various types of glaucoma, and its influence on intraocular pressure (IOP) measurement.
METHODS—Central corneal thickness (CCT) was determined by using OCT in 167 subjects (167 eyes). 20 had primary open angle glaucoma (POAG), 42 had low tension glaucoma (LTG), 22 had ocular hypertension (OHT), 10 had primary angle closure glaucoma (AC), 24 had pseudoexfoliation glaucoma (PEX), 13 had pigmentary glaucoma (PIG), and 36 were normal.
RESULTS—CCT was significantly higher in ocular hypertensive subjects (593 (SD 35) µm, p <0.0001) than in the controls (530 (32) µm), whereas patients with LTG (482 (28) µm, p < 0.0001), PEX (493 (33) µm, p <0.0001), and POAG (512 (30) µm, p <0.05) showed significantly lower readings. There was no statistically significant difference between the controls and patients with PIG (510 (39) µm) and AC (539 (37) µm).
CONCLUSIONS—Because of thinner CCT in patients with LTG, PEX, and POAG this may result in underestimation of IOP, whereas thicker corneas may lead to an overestimation of IOP in subjects with OH. By determining CCT with OCT, a new and precise technique to measure CCT, this study emphasises the need for a combined measurement of IOP and CCT in order to obtain exact IOP readings.


doi:10.1136/bjo.84.11.1233
PMCID: PMC1723313  PMID: 11049946
23.  Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma 
The principal purpose of this study was to describe a model of canine hereditary angle-closure glaucoma characterized by progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss.
Purpose.
To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma.
Methods.
Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU).
Results.
A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 ± 0.4 μV; control, 6.2 ± 0.3 μV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa.
Conclusions.
Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss.
doi:10.1167/iovs.09-4081
PMCID: PMC3258664  PMID: 19661222
24.  Iridoschisis: case report and review of the literature 
Iridoschisis is a rare condition that consists of the separation of the anterior mesodermic layer of the iris. In more than two-thirds of cases it is associated with glaucoma. We report the case of an 80-year-old patient who had bilateral iridoschisis and presented with acute angle-closure glaucoma. The patient was free from a history of ocular trauma or of heritable ocular disease. Chronic open-angle glaucoma, as well as intermittent angle-closure glaucoma, should be excluded in all patients with iridoschisis, and regular follow-up should be established upon diagnosis of the entity.
doi:10.2147/OPTH.S17269
PMCID: PMC3076110  PMID: 21499560
iridoschisis; angle-closure glaucoma; iris degeneration
25.  Pigment dispersion syndrome: a clinical study. 
This study involved a group of 407 patients (799 eyes) with pigment dispersion syndrome gathered from a glaucoma population of 9200 patients. The sex distribution was equal. The majority (65%) of patients were myopic. The incidence of retinal detachment was 6.4%. No patients were black, but 5 were mulatto. Approximately one-quarter of the patients wih pigment dispersion syndrome (31% of the men, 19% of the women) had glaucoma. The average age of onset of glaucoma was 15 years less than in control patients with chronic simple glaucoma. When both eyes were affected by glaucoma, the glaucoma was consistently more severe in the eye with the more heavily pigmented angle. The degree of iris transillumination was found to be of no importance in predicting the presence of glaucoma or the severity of trabecular pigmentation. The pressure in 66% of the eyes with pigmentary glaucoma was controlled medically. A higher percentage of patients with pigmentary glaucoma required surgery than patients in the control group with chronic simple glaucoma. Men with pigmentary glaucoma required surgery at a much earlier age than women with pigmentary glaucoma.
PMCID: PMC1039495  PMID: 7236571

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